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image of Schisanhenol Inhibits the Proliferation of Hepatocellular Carcinoma Cells by Targeting Programmed Cell Death-ligand 1 via the STAT3 Pathways

Abstract

Background

Programmed cell death-ligand 1 (PD-L1) is overexpressed in tumor cells, which promotes tumor cell survival and cell proliferation and causes tumor cells to escape T-cell killing. Schisanhenol, a biphenyl cyclooctene lignin-like compound, was extracted and isolated from the plant named .

Purpose

In this work, we studied the anticancer potential of schisanhenol and explored whether schisanhenol mediated its effect by inhibiting the expression of PD-L1 and .

Materials and Methods

we performed western blot, immunofluorescence, immunoprecipitation, and colony formation assays to study the proteins, genes, and pathways related to the anti-tumour activity of schisanhenol. we explored the antitumor activity of schisanhenol through orthotopic liver transplantation and subcutaneous transplantation tumor models of hepatocellular carcinoma (HCC) cells.

Results

We found that schisanhenol decreased the viability of HCC cells. It inhibited the expression of programmed cell death ligand-1 (PD-L1), which plays a pivotal role in tumorigenesis. Subsequently, schisanhenol suppressed the expression of PD-L1 by decreasing the activation of STAT3. Furthermore, we found that schisanhenol inhibited the activation of STAT3 JAK/STAT3 (T705), Src/STAT3 (T705), and PI3K/AKT/mTOR/STAT3 (S727) pathways. Colony formation tests showed that schisanhenol suppressed cell proliferation by inhibiting PD-L1. Schisanhenol also enhanced cytotoxic T lymphocytes (CTL) activity and regained their ability to kill tumour cells in co-culture. Finally, observation confirmed the antitumor activity of schisanhenol.

Conclusion

Schisanhenol inhibits the proliferation of HCC cells by targeting PD-L1 the STAT3 pathways. These findings prove that schisanhenol is a valuable candidate for HCC therapeutics and reveal previously unknown characteristics of schisanhenol.

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2025-01-10
2025-04-02

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References

  1. Siegel R.L. Miller K.D. Jemal A. Cancer statistics, 2020. CA Cancer J. Clin. 2020 70 1 7 30 10.3322/caac.21590 31912902
    [Google Scholar]
  2. Llovet J.M. Zucman-Rossi J. Pikarsky E. Sangro B. Schwartz M. Sherman M. Gores G. Hepatocellular carcinoma. Nat. Rev. Dis. Primers 2016 2 1 16018 10.1038/nrdp.2016.18 27158749
    [Google Scholar]
  3. Villanueva A. Hepatocellular Carcinoma. N. Engl. J. Med. 2019 380 15 1450 1462 10.1056/NEJMra1713263 30970190
    [Google Scholar]
  4. El-Khoueiry A.B. Sangro B. Yau T. Crocenzi T.S. Kudo M. Hsu C. Kim T.Y. Choo S.P. Trojan J. Welling T.H. III Meyer T. Kang Y.K. Yeo W. Chopra A. Anderson J. dela Cruz C. Lang L. Neely J. Tang H. Dastani H.B. Melero I. Nivolumab in patients with advanced hepatocellular carcinoma (CheckMate 040): An open-label, non-comparative, phase 1/2 dose escalation and expansion trial. Lancet 2017 389 10088 2492 2502 10.1016/S0140‑6736(17)31046‑2 28434648
    [Google Scholar]
  5. Kambhampati S. Bauer K.E. Bracci P.M. Keenan B.P. Behr S.C. Gordan J.D. Kelley R.K. Nivolumab in patients with advanced hepatocellular carcinoma and Child‐Pugh class B cirrhosis: Safety and clinical outcomes in a retrospective case series. Cancer 2019 125 18 3234 3241 10.1002/cncr.32206 31154669
    [Google Scholar]
  6. Freeman G.J. Long A.J. Iwai Y. Bourque K. Chernova T. Nishimura H. Fitz L.J. Malenkovich N. Okazaki T. Byrne M.C. Horton H.F. Fouser L. Carter L. Ling V. Bowman M.R. Carreno B.M. Collins M. Wood C.R. Honjo T. Engagement of the PD-1 immunoinhibitory receptor by a novel B7 family member leads to negative regulation of lymphocyte activation. J. Exp. Med. 2000 192 7 1027 1034 10.1084/jem.192.7.1027 11015443
    [Google Scholar]
  7. Butte M.J. Keir M.E. Phamduy T.B. Sharpe A.H. Freeman G.J. Programmed death-1 ligand 1 interacts specifically with the B7-1 costimulatory molecule to inhibit T cell responses. Immunity 2007 27 1 111 122 10.1016/j.immuni.2007.05.016 17629517
    [Google Scholar]
  8. Baumeister S.H. Freeman G.J. Dranoff G. Sharpe A.H. Coinhibitory pathways in immunotherapy for cancer. Annu. Rev. Immunol. 2016 34 1 539 573 10.1146/annurev‑immunol‑032414‑112049 26927206
    [Google Scholar]
  9. Qianzi L Min X Mengjie Q Junhan Y Qu W Yi Z Qingqing L Xueding C Lehe Y Haiyang Z Chengguang Z Xiaona XJP Solamargine improves the therapeutic efficacy of anti-PD-L1 in lung adenocarcinoma by inhibiting STAT1 activation. Phytomedicine 2024 128 155538
    [Google Scholar]
  10. Xiang X. Yu P.C. Long D. Liao X.L. Zhang S. You X.M. Zhong J.H. Li L.Q. Prognostic value of PD -L1 expression in patients with primary solid tumors. Oncotarget 2018 9 4 5058 5072 10.18632/oncotarget.23580 29435162
    [Google Scholar]
  11. Xixi Z. Mengjie L. Chaofan L. Xiaoxiao L. Jiaqi Z. Hongbing M. Shuqun Z. Jingkun QJII. High dose Vitamin C inhibits PD-L1 by ROS-pSTAT3 signal pathway and enhances T cell function in TNBC Int Immunopharmacol 2024 126 111321
    [Google Scholar]
  12. Clark C.A. Gupta H.B. Sareddy G. Pandeswara S. Lao S. Yuan B. Drerup J.M. Padron A. Conejo-Garcia J. Murthy K. Liu Y. Turk M.J. Thedieck K. Hurez V. Li R. Vadlamudi R. Curiel T.J. Tumor-intrinsic PD-L1 signals regulate cell growth, pathogenesis, and autophagy in ovarian cancer and melanoma. Cancer Res. 2016 76 23 6964 6974 10.1158/0008‑5472.CAN‑16‑0258 27671674
    [Google Scholar]
  13. Song J. Wang J. Tian S. Li H. Discovery of STAT3 inhibitors: Recent advances and future perspectives. Curr. Med. Chem. 2023 30 16 1824 1847 10.2174/0929867329666220819093117 35986534
    [Google Scholar]
  14. El-Tanani M. Al Khatib A.O. Aladwan S.M. Abuelhana A. McCarron P.A. Tambuwala M.M. Importance of STAT3 signalling in cancer, metastasis and therapeutic interventions. Cell. Signal. 2022 92 110275 10.1016/j.cellsig.2022.110275 35122990
    [Google Scholar]
  15. Wang Z. Li M.Y. Zhang Z.H. Zuo H.X. Wang J.Y. Xing Y. Ri M. Jin H.L. Jin C.H. Xu G.H. Piao L.X. Jiang C.G. Ma J. Jin X. Panaxadiol inhibits programmed cell death-ligand 1 expression and tumour proliferation via hypoxia-inducible factor (HIF)-1α and STAT3 in human colon cancer cells. Pharmacol. Res. 2020 155 104727 10.1016/j.phrs.2020.104727 32113874
    [Google Scholar]
  16. Xiao D. Zeng T. Zhu W. Yu Z.Z. Huang W. Yi H. Lu S.S. Feng J. Feng X.P. Wu D. Wen Q. Zhou J.H. Yuan L. Zhuang W. Xiao Z.Q. ANXA1 promotes tumor immune evasion by binding parp1 and upregulating Stat3-induced expression of PD-L1 in multiple cancers. Cancer Immunol. Res. 2023 11 10 1367 1383 10.1158/2326‑6066.CIR‑22‑0896 37566399
    [Google Scholar]
  17. Zhang Z.H. Li M.Y. Wang Z. Zuo H.X. Wang J.Y. Xing Y. Jin C. Xu G. Piao L. Piao H. Ma J. Jin X. Convallatoxin promotes apoptosis and inhibits proliferation and angiogenesis through crosstalk between JAK2/STAT3 (T705) and mTOR/STAT3 (S727) signaling pathways in colorectal cancer. Phytomedicine 2020 68 153172 10.1016/j.phymed.2020.153172 32004989
    [Google Scholar]
  18. Huang G. Yan H. Ye S. Tong C. Ying Q.L. STAT3 phosphorylation at tyrosine 705 and serine 727 differentially regulates mouse ESC fates. Stem Cells 2014 32 5 1149 1160 10.1002/stem.1609 24302476
    [Google Scholar]
  19. Koh J. Jang J.Y. Keam B. Kim S. Kim M.Y. Go H. Kim T.M. Kim D.W. Kim C.W. Jeon Y.K. Chung D.H. EML4-ALK enhances programmed cell death-ligand 1 expression in pulmonary adenocarcinoma via hypoxia-inducible factor (HIF)-1α and STAT3. OncoImmunology 2016 5 3 e1108514 10.1080/2162402X.2015.1108514 27141364
    [Google Scholar]
  20. Jahangiri A. Dadmanesh M. Ghorban K. STAT3 inhibition reduced PD‐L1 expression and enhanced antitumor immune responses. J. Cell. Physiol. 2020 235 12 9457 9463 10.1002/jcp.29750 32401358
    [Google Scholar]
  21. Wang W.Y. Chen J.G. Pharmacological effects and development research of Schisandra chinensis BeihuaUniv. (Nature) 2007 128 133
    [Google Scholar]
  22. Kim H.S. Lee J.H. Park H.S. Lee G.S. Kim H.W. Ha K.T. Kim B.J. Schizandra chinensis extracts induce apoptosis in human gastric cancer cells via JNK/p38 MAPK activation and the ROS-mediated/mitochondria-dependent pathway. Pharm. Biol. 2015 53 2 212 219 10.3109/13880209.2014.913297 25243868
    [Google Scholar]
  23. Zhu P.L. Li J.K. Jiang X.L. Zhang S.Q. Zhang Z. Wang Y. Zhang Z. Chen W.Q. Yung K.K.L. A traditional prescription comprising Astragali Radix and Schisandra chinensis Fructus induces apoptosis and protective autophagy in hepatocellular carcinoma cells. J. Ethnopharmacol. 2023 312 116548 10.1016/j.jep.2023.116548 37100264
    [Google Scholar]
  24. Olas B. Cardioprotective potential of berries of Schisandra chinensis Turcz. (Baill.), their components and food products. Nutrients 2023 15 3 592 10.3390/nu15030592 36771299
    [Google Scholar]
  25. Chiu T.H. Ku C.W. Ho T.J. Tsai K.L. Yang Y.D. Ou H.C. Chen H.I. Schisanhenol ameliorates oxLDL ‐caused endothelial dysfunction by inhibiting LOX ‐1 signaling. Environ. Toxicol. 2023 38 7 1589 1596 10.1002/tox.23788 36999521
    [Google Scholar]
  26. Li B. Xiao Q. Zhao H. Zhang J. Yang C. Zou Y. Zhang B. Liu J. Sun H. Liu H. Schisanhenol ameliorates non-alcoholic fatty liver disease via inhibiting miR-802 activation of AMPK-mediated modulation of hepatic lipid metabolism. Acta Pharm. Sin. B 2024 14 9 3949 3963 10.1016/j.apsb.2024.05.014 39309511
    [Google Scholar]
  27. Yang H. Li L. Jiao Y. Zhang Y. Wang Y. Zhu K. Sun C. Thioredoxin-1 mediates neuroprotection of Schisanhenol against MPP+-induced apoptosis via suppression of ASK1-P38-NF-κB pathway in SH-SY5Y cells. Sci. Rep. 2021 11 1 21604 10.1038/s41598‑021‑01000‑3 34732784
    [Google Scholar]
  28. Zhang Z.H. Mi C. Wang K.S. Wang Z. Li M.Y. Zuo H.X. Xu G.H. Li X. Piao L.X. Ma J. Jin X. Chelidonine inhibits TNF‐α‐induced inflammation by suppressing the NF‐κB pathways in HCT116 cells. Phytother. Res. 2018 32 1 65 75 10.1002/ptr.5948 29044876
    [Google Scholar]
  29. Zhang Z. Li M. Tai Y. Xing Y. Zuo H. Jin X. Ma J. ZNF70 regulates IL-1β secretion of macrophages to promote the proliferation of HCT116 cells via activation of NLRP3 inflammasome and STAT3 pathway in colitis-associated colorectal cancer. Cell. Signal. 2024 114 110979 10.1016/j.cellsig.2023.110979 38000525
    [Google Scholar]
  30. Zhang Y.F. Zhang Z.H. Li M.Y. Wang J.Y. Xing Y. Ri M. Jin C.H. Xu G.H. Piao L.X. Zuo H.X. Jin H.L. Ma J. Jin X. Britannin stabilizes T cell activity and inhibits proliferation and angiogenesis by targeting PD-L1 via abrogation of the crosstalk between Myc and HIF-1α in cancer. Phytomedicine 2021 81 153425 10.1016/j.phymed.2020.153425 33310309
    [Google Scholar]
  31. Zhang Z.H. Wang C.M. Li H. Sun J.H. Zhang C.Y. Chen J.G. Astragaloside IV inhibits proliferation and migration of lung cancer cells through JAK/STAT3 signaling pathway. BeihuaUniv.(Nature) 2022 23 775 779
    [Google Scholar]
  32. Wen S. An R. Li D. Cao J. Li Z. Zhang W. Chen R. Li Q. Lai X. Sun L. Sun S. Tea and Citrus maxima complex induces apoptosis of human liver cancer cells via PI3K/AKT/mTOR pathway in vitro. Chin. Herb. Med. 2022 14 3 449 458 10.1016/j.chmed.2021.09.015 36118010
    [Google Scholar]
  33. Liu X. Xing Y. Li M. Zhang Z. Wang J. Ri M. Jin C. Xu G. Piao L. Jin H. Zuo H. Ma J. Jin X. Licochalcone A inhibits proliferation and promotes apoptosis of colon cancer cell by targeting programmed cell death-ligand 1 via the NF-κB and Ras/Raf/MEK pathways. J. Ethnopharmacol. 2021 273 113989 10.1016/j.jep.2021.113989 33677006
    [Google Scholar]
  34. Jin Y. Zuo H.X. Li M.Y. Zhang Z.H. Xing Y. Wang J.Y. Ma J. Li G. Piao H. Gu P. Jin X. Anti-tumor effects of Carrimycin and Monomeric Isovalerylspiramycin I on hepatocellular carcinoma in vitro and in vivo. Front. Pharmacol. 2021 12 774231 10.3389/fphar.2021.774231 34899336
    [Google Scholar]
  35. Wang Y. Chen Z. Luo J. Zhang J. Sang A. Cheng Z. Li X. Salidroside postconditioning attenuates ferroptosis-mediated lung ischemia-reperfusion injury by activating the Nrf2/SLC7A11 signaling axis. Int. Immunopharmacol. 2023 115 109731 10.1016/j.intimp.2023.109731 36907990
    [Google Scholar]
  36. Wang J.Y. Jiang M.W. Li M.Y. Zhang Z.H. Xing Y. Ri M. Jin C.H. Xu G.H. Piao L.X. Jin H.L. Ma J. Jin Y. Zuo H.X. Jin X. Formononetin represses cervical tumorigenesis by interfering with the activation of PD-L1 through MYC and STAT3 downregulation. J. Nutr. Biochem. 2022 100 108899 10.1016/j.jnutbio.2021.108899 34748924
    [Google Scholar]
  37. Chen J. Jiang C.C. Jin L. Zhang X.D. Regulation of PD-L1: A novel role of pro-survival signalling in cancer. Ann. Oncol. 2016 27 3 409 416 10.1093/annonc/mdv615 26681673
    [Google Scholar]
  38. Xie C. Zhou X. Liang C. Li X. Ge M. Chen Y. Yin J. Zhu J. Zhong C. Apatinib triggers autophagic and apoptotic cell death via VEGFR2/STAT3/PD-L1 and ROS/Nrf2/p62 signaling in lung cancer. J. Exp. Clin. Cancer Res. 2021 40 1 266 10.1186/s13046‑021‑02069‑4 34429133
    [Google Scholar]
  39. Shen M. Xu Z. Xu W. Jiang K. Zhang F. Ding Q. Xu Z. Chen Y. Inhibition of ATM reverses EMT and decreases metastatic potential of cisplatin-resistant lung cancer cells through JAK/STAT3/PD-L1 pathway. J. Exp. Clin. Cancer Res. 2019 38 1 149 10.1186/s13046‑019‑1161‑8 30961670
    [Google Scholar]
  40. Tong L. Li J. Li Q. Wang X. Medikonda R. Zhao T. Li T. Ma H. Yi L. Liu P. Xie Y. Choi J. Yu S. Lin Y. Dong J. Huang Q. Jin X. Lim M. Yang X. ACT001 reduces the expression of PD-L1 by inhibiting the phosphorylation of STAT3 in glioblastoma. Theranostics 2020 10 13 5943 5956 10.7150/thno.41498 32483429
    [Google Scholar]
  41. Lee J.H. Kim C. Kim S.H. Sethi G. Ahn K.S. Farnesol inhibits tumor growth and enhances the anticancer effects of bortezomib in multiple myeloma xenograft mouse model through the modulation of STAT3 signaling pathway. Cancer Lett. 2015 360 2 280 293 10.1016/j.canlet.2015.02.024 25697480
    [Google Scholar]
  42. Proietti C. Salatino M. Rosemblit C. Carnevale R. Pecci A. Kornblihtt A.R. Molinolo A.A. Frahm I. Charreau E.H. Schillaci R. Elizalde P.V. Progestins induce transcriptional activation of signal transducer and activator of transcription 3 (Stat3) via a Jak- and Src-dependent mechanism in breast cancer cells. Mol. Cell. Biol. 2005 25 12 4826 4840 10.1128/MCB.25.12.4826‑4840.2005 15923602
    [Google Scholar]
  43. Wei J. Ma L. Li C. Pierson C.R. Finlay J.L. Lin J. Targeting upstream Kinases of STAT3 in human Medulloblastoma cells. Curr. Cancer Drug Targets 2019 19 7 571 582 10.2174/1568009618666181016165604 30332965
    [Google Scholar]
  44. Yokogami K. Wakisaka S. Avruch J. Reeves S.A. Serine phosphorylation and maximal activation of STAT3 during CNTF signaling is mediated by the rapamycin target mTOR. Curr. Biol. 2000 10 1 47 50 10.1016/S0960‑9822(99)00268‑7 10660304
    [Google Scholar]
  45. Yang A. Li M.Y. Zhang Z.H. Wang J.Y. Xing Y. Ri M. Jin C.H. Xu G.H. Piao L.X. Jin H.L. Zuo H.X. Ma J. Jin X. Erianin regulates programmed cell death ligand 1 expression and enhances cytotoxic T lymphocyte activity. J. Ethnopharmacol. 2021 273 113598 10.1016/j.jep.2020.113598 33220359
    [Google Scholar]
  46. Wang Y. Zhang C. Yan M. Ma X. Song L. Wang B. Li P. Liu P. PD‐L1 regulates tumor proliferation and T‐cell function in NF2‐associated meningiomas. CNS Neurosci. Ther. 2024 30 6 e14784 10.1111/cns.14784 38828669
    [Google Scholar]
  47. Madhi H. Lee J.S. Choi Y.E. Li Y. Kim M.H. Choi Y. Goh S.H. FOXM1 inhibition enhances the therapeutic outcome of lung cancer immunotherapy by modulating PD‐L1 expression and cell proliferation. Adv. Sci. (Weinh.) 2022 9 29 2202702 10.1002/advs.202202702 35975458
    [Google Scholar]
  48. Du W. Zhu J. Zeng Y. Liu T. Zhang Y. Cai T. Fu Y. Zhang W. Zhang R. Liu Z. Huang J. KPNB1-mediated nuclear translocation of PD-L1 promotes non-small cell lung cancer cell proliferation via the Gas6/MerTK signaling pathway. Cell Death Differ. 2021 28 4 1284 1300 10.1038/s41418‑020‑00651‑5 33139930
    [Google Scholar]
  49. Soltani M. Vosoughi M. Ganjalikhani-Hakemi M. Shapoorian H. Beshkar P. Eskandari N. Ghezelbash B. PD-1/PD-L1 interaction regulates BCL2, KI67, BAX, and CASP3, altering proliferation, survival, and Apoptosis in Acute Myeloid Leukemia. Iran. J. Allergy Asthma Immunol. 2023 22 5 495 503 10.18502/ijaai.v22i5.13998 38085150
    [Google Scholar]
  50. Juneja V.R. McGuire K.A. Manguso R.T. LaFleur M.W. Collins N. Haining W.N. Freeman G.J. Sharpe A.H. PD-L1 on tumor cells is sufficient for immune evasion in immunogenic tumors and inhibits CD8 T cell cytotoxicity. J. Exp. Med. 2017 214 4 895 904 10.1084/jem.20160801 28302645
    [Google Scholar]
  51. Liang L. Li Y. Jiao Y. Zhang C. Shao M. Jiang H. Wu Z. Chen H. Guo J. Jia H. Zhao T. Maprotiline prompts an antitumour effect by inhibiting PD-L1 expression in mice with melanoma. Curr. Mol. Pharmacol. 2023 17 1 e18761429259562 10.2174/0118761429259562230925055749 37982288
    [Google Scholar]
  52. Huang D. Wang X. Qian Y. Wu J. Chen B. Zhang D. Dong F. Li Y. MAX transcriptionally enhances PD-L1 to inhibit CD8+ T cell-mediated killing of lung adenocarcinoma cells. Cell. Immunol. 2023 386 104706 10.1016/j.cellimm.2023.104706 36931054
    [Google Scholar]
  53. Kudo M. Immune checkpoint inhibition in hepatocellular Carcinoma: Basics and ongoing clinical trials. Oncology 2017 92 Suppl. 1 50 62 10.1159/000451016 28147363
    [Google Scholar]
  54. Wen W. Zhang Y. Zhang H. Chen Y. Clinical outcomes of PD-1/PD-L1 inhibitors in patients with advanced hepatocellular carcinoma: A systematic review and meta-analysis. J. Cancer Res. Clin. Oncol. 2023 149 3 969 978 10.1007/s00432‑022‑04057‑3 35771261
    [Google Scholar]
  55. Voutsadakis I.A. PD-1 inhibitors monotherapy in hepatocellular carcinoma: Meta-analysis and systematic review. Hepatobiliary Pancreat. Dis. Int. 2019 18 6 505 510 10.1016/j.hbpd.2019.09.007 31551142
    [Google Scholar]
  56. Feun L.G. Li Y.Y. Wu C. Wangpaichitr M. Jones P.D. Richman S.P. Madrazo B. Kwon D. Garcia-Buitrago M. Martin P. Hosein P.J. Savaraj N. Phase 2 study of pembrolizumab and circulating biomarkers to predict anticancer response in advanced, unresectable hepatocellular carcinoma. Cancer 2019 125 20 3603 3614 10.1002/cncr.32339 31251403
    [Google Scholar]
  57. Jiang Y. Chen M. Nie H. Yuan Y. PD-1 and PD-L1 in cancer immunotherapy: Clinical implications and future considerations. Hum. Vaccin. Immunother. 2019 15 5 1111 1122 10.1080/21645515.2019.1571892 30888929
    [Google Scholar]
  58. Doroshow D.B. Bhalla S. Beasley M.B. Sholl L.M. Kerr K.M. Gnjatic S. Wistuba I.I. Rimm D.L. Tsao M.S. Hirsch F.R. PD-L1 as a biomarker of response to immune-checkpoint inhibitors. Nat. Rev. Clin. Oncol. 2021 18 6 345 362 10.1038/s41571‑021‑00473‑5 33580222
    [Google Scholar]
  59. Geng Q. Jiao P. Jin P. Su G. Dong J. Yan B. PD-1/PD-L1 inhibitors for immuno-oncology: From antibodies to small molecules. Curr. Pharm. Des. 2018 23 39 6033 6041 10.2174/1381612823666171004120152 28982322
    [Google Scholar]
  60. Zhang M. Li G. Wang Y. Wang Y. Zhao S. Haihong P. Zhao H. Wang Y. PD-L1 expression in lung cancer and its correlation with driver mutations: A meta-analysis. Sci. Rep. 2017 7 1 10255 10.1038/s41598‑017‑10925‑7 28860576
    [Google Scholar]
  61. Yang J. Hu L. Immunomodulators targeting the PD‐1/PD‐L1 protein‐protein interaction: From antibodies to small molecules. Med. Res. Rev. 2019 39 1 265 301 10.1002/med.21530 30215856
    [Google Scholar]
  62. Chames P. Van Regenmortel M. Weiss E. Baty D. Therapeutic antibodies: Successes, limitations and hopes for the future. Br. J. Pharmacol. 2009 157 2 220 233 10.1111/j.1476‑5381.2009.00190.x 19459844
    [Google Scholar]
  63. Kothari M. Wanjari A. Acharya S. Karwa V. Chavhan R. Kumar S. Kadu A. Patil R. A comprehensive review of monoclonal antibodies in modern medicine: Tracing the evolution of a revolutionary therapeutic approach. Cureus 2024 16 6 e61983 10.7759/cureus.61983 38983999
    [Google Scholar]
  64. Herbst R.S. Soria J.C. Kowanetz M. Fine G.D. Hamid O. Gordon M.S. Sosman J.A. McDermott D.F. Powderly J.D. Gettinger S.N. Kohrt H.E.K. Horn L. Lawrence D.P. Rost S. Leabman M. Xiao Y. Mokatrin A. Koeppen H. Hegde P.S. Mellman I. Chen D.S. Hodi F.S. Predictive correlates of response to the anti-PD-L1 antibody MPDL3280A in cancer patients. Nature 2014 515 7528 563 567 10.1038/nature14011 25428504
    [Google Scholar]
  65. Chen J. Zhao Y. Wang X. Zang L. Yin D. Tan S. Hyperoside inhibits RNF8-mediated nuclear translocation of β-catenin to repress PD-L1 expression and prostate cancer. Anticancer. Agents Med. Chem. 2024 24 6 464 476 10.2174/0118715206289246240110044931 38305391
    [Google Scholar]
  66. Fankhauser C.D. Curioni-Fontecedro A. Allmann V. Beyer J. Tischler V. Sulser T. Moch H. Bode P.K. Frequent PD-L1 expression in testicular germ cell tumors. Br. J. Cancer 2015 113 3 411 413 10.1038/bjc.2015.244 26171934
    [Google Scholar]
  67. Aggarwal B.B. Sethi G. Ahn K.S. Sandur S.K. Pandey M.K. Kunnumakkara A.B. Sung B. Ichikawa H. Targeting signal-transducer-and-activator-of-transcription-3 for prevention and therapy of cancer: Modern target but ancient solution. Ann. N. Y. Acad. Sci. 2006 1091 1 151 169 10.1196/annals.1378.063 17341611
    [Google Scholar]
  68. Atsaves V. Tsesmetzis N. Chioureas D. Kis L. Leventaki V. Drakos E. Panaretakis T. Grander D. Medeiros L.J. Young K.H. Rassidakis G.Z. PD-L1 is commonly expressed and transcriptionally regulated by STAT3 and MYC in ALK-negative anaplastic large-cell lymphoma. Leukemia 2017 31 7 1633 1637 10.1038/leu.2017.103 28344319
    [Google Scholar]
  69. Wang X. Crowe P.J. Goldstein D. Yang J.L. STAT3 inhibition, a novel approach to enhancing targeted therapy in human cancers. Int. J. Oncol. 2012 41 4 1181 1191 10.3892/ijo.2012.1568 22842992
    [Google Scholar]
  70. Lee H. Jeong A.J. Ye S.K. Highlighted STAT3 as a potential drug target for cancer therapy. BMB Rep. 2019 52 7 415 423 10.5483/BMBRep.2019.52.7.152 31186087
    [Google Scholar]
  71. Decker T. Kovarik P. Serine phosphorylation of STATs. Oncogene 2000 19 21 2628 2637 10.1038/sj.onc.1203481 10851062
    [Google Scholar]
  72. Ouédraogo Z.G. Müller-Barthélémy M. Kemeny J.L. Dedieu V. Biau J. Khalil T. Raoelfils L.I. Granzotto A. Pereira B. Beaudoin C. Guissou I.P. Berger M. Morel L. Chautard E. Verrelle P. STAT3 Serine 727 Phosphorylation: A Relevant target to radiosensitize human glioblastoma. Brain Pathol. 2016 26 1 18 30 10.1111/bpa.12254 25736961
    [Google Scholar]
  73. Cao Y. Zhang L. Kamimura Y. Ritprajak P. Hashiguchi M. Hirose S. Azuma M. B7-H1 overexpression regulates epithelial-mesenchymal transition and accelerates carcinogenesis in skin. Cancer Res. 2011 71 4 1235 1243 10.1158/0008‑5472.CAN‑10‑2217 21159661
    [Google Scholar]
  74. Yiping L. Miao Y. Jinsheng Y. Yankai L. Jianxin G. Zhen J. Jie WJAAMC. Sauchinone inhibits the proliferation and immune invasion capacity of colorectal cancer cells through the suppression of PD-L1 and MMP2/MM9 Anticancer Agents Med Chem 2023 23 12 1406 1414
    [Google Scholar]
  75. Jeong H. Koh J. Kim S. Song S.G. Lee S.H. Jeon Y. Lee C.H. Keam B. Lee S.H. Chung D.H. Jeon Y.K. Epithelial−mesenchymal transition induced by tumor cell-intrinsic PD-L1 signaling predicts a poor response to immune checkpoint inhibitors in PD-L1-high lung cancer. Br. J. Cancer 2024 131 1 23 36 10.1038/s41416‑024‑02698‑4 38729997
    [Google Scholar]
/content/journals/acamc/10.2174/0118715206349131241121091834
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Schisanhenol Inhibits the Proliferation of Hepatocellular Carcinoma Cells by Targeting Programmed Cell Death-ligand 1 via the STAT3 Pathways
Bentham Science Publishers ; https://doi.org/10.2174/0118715206349131241121091834
/content/journals/acamc/10.2174/0118715206349131241121091834
/content/journals/acamc/10.2174/0118715206349131241121091834
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  • Article Type:     Research Article
Keywords: hepatocellular carcinoma ; PD-L1 ; Schisanhenol ; immune escape ; proliferation ; STAT3

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