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2000
Volume 33, Issue 2
  • ISSN: 0929-8673
  • E-ISSN: 1875-533X

Abstract

Background

Lung cancer (LC) is the second most lethal cancer and efficient treatments are missing. Our understanding of the underlying pathogenic mechanisms remains limited. Oridonin is a compound extracted from the Chinese herb with anticancer properties. Nevertheless, its effects on LC and the underlying mechanisms remain unknown.

Methods

In the current research, A549 and Hcc1833 cells were treated with different doses of oridonin, and cell proliferation and migration were detected using CCK8, EdU, Transwell, and wound healing assays. A subcutaneous tumor and caudal vein metastasis model was generated to verify the inhibitory effects of oridonin on Hcc1833 tumor growth and metastasis . Proteomics analyses then were performed to examine the regulatory mechanism. LiP-SMap combined with microscale thermophoresis and molecular docking analyses were used to validate the relationship between oridonin and S100A11.

Results

Data showed that oridonin suppressed cell proliferation and migration depending on dose and suppressed tumor growth and invasion. LiP-SMap and molecular docking analyses confirmed that oridonin interacted with the Asn-53 residue of S100A11, which inhibited the activation of oridonin. S100A11 overexpression reversed the inhibitory effects of oridonin on cell proliferation and migration.

Conclusion

In conclusion, the data indicate that oridonin suppresses LC malignant progression by targeting S100A11.

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2025-01-23
2026-02-11
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References

  1. BrayF. FerlayJ. SoerjomataramI. SiegelR.L. TorreL.A. JemalA. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries.CA Cancer J. Clin.201868639442410.3322/caac.2149230207593
    [Google Scholar]
  2. MegyesfalviZ. GayC.M. PopperH. PirkerR. OstorosG. HeekeS. LangC. HoetzeneckerK. SchwendenweinA. BoettigerK. BunnP.A.Jr Renyi-VamosF. SchelchK. ProschH. ByersL.A. HirschF.R. DomeB. Clinical insights into small cell lung cancer: Tumor heterogeneity, diagnosis, therapy, and future directions.CA Cancer J. Clin.202373662065210.3322/caac.2178537329269
    [Google Scholar]
  3. HwangT.L. ChangC.H. Oridonin enhances cytotoxic activity of natural killer cells against lung cancer.Int. Immunopharmacol.202312211066910.1016/j.intimp.2023.11066937480753
    [Google Scholar]
  4. LeiterA. VeluswamyR.R. WisniveskyJ.P. The global burden of lung cancer: Current status and future trends.Nat. Rev. Clin. Oncol.202320962463910.1038/s41571‑023‑00798‑337479810
    [Google Scholar]
  5. LiuD.L. BuH.Q. WangW.L. LuoH. ChengB.N. Oridonin enhances the anti-tumor activity of gemcitabine towards pancreatic cancer by stimulating Bax- and Smac-dependent apoptosis.Transl. Cancer Res.2020974148416110.21037/tcr‑19‑300035117784
    [Google Scholar]
  6. WangY. LvH. DaiC. WangX. YinY. ChenZ. Oridonin dose-dependently modulates the cell senescence and apoptosis of gastric cancer cells.Evid. Based Complement. Alternat. Med.2021202111210.1155/2021/502353634795783
    [Google Scholar]
  7. ZhouJ. LiY. ShiX. HaoS. ZhangF. GuoZ. GaoY. GuoH. LiuL. Oridonin inhibits tumor angiogenesis and induces vessel normalization in experimental colon cancer.J. Cancer202112113257326410.7150/jca.5592933976735
    [Google Scholar]
  8. ZhaoY. XiaoW. PengW. HuangQ. WuK. EvansC.E. LiuX. JinH. Oridonin-Loaded nanoparticles inhibit breast cancer progression through regulation of ROS-related Nrf2 signaling pathway.Front. Bioeng. Biotechnol.2021960057910.3389/fbioe.2021.60057933898397
    [Google Scholar]
  9. XuL. BiY. XuY. ZhangZ. XuW. ZhangS. ChenJ. Oridonin inhibits the migration and epithelial- to-mesenchymal transition of small cell lung cancer cells by suppressing FAK-ERK1/2 signalling pathway.J. Cell. Mol. Med.20202484480449310.1111/jcmm.1510632168416
    [Google Scholar]
  10. YangH. GaoY. FanX. LiuX. PengL. CiX. Oridonin sensitizes cisplatin-induced apoptosis via AMPK/Akt/mTOR-dependent autophagosome accumulation in A549 cells.Front. Oncol.2019976910.3389/fonc.2019.0076931475112
    [Google Scholar]
  11. LiW. HanF. TangK. DingC. XiongF. XiaoY. LiC. LiangQ. LeeK.Y. LeeI.S. GaoH. Inhibiting NF-κB-S100A11 signaling and targeting S100A11 for anticancer effects of demethylzeylasteral in human colon cancer.Biomed. Pharmacother.202316811572510.1016/j.biopha.2023.11572537879212
    [Google Scholar]
  12. ZhengM. MengH. LiY. ShiJ. HanY. ZhaoC. ChenJ. HanJ. LiangJ. ChenY. LiuQ. WangY. S100A11 promotes metastasis via AKT and ERK signaling pathways and has a diagnostic role in hepatocellular carcinoma.Int. J. Med. Sci.202320331832810.7150/ijms.8050336860671
    [Google Scholar]
  13. YangH. LvH. LiH. CiX. PengL. Oridonin protects LPS-induced acute lung injury by modulating Nrf2- mediated oxidative stress and Nrf2-independent NLRP3 and NF-κB pathways.Cell Commun. Signal.20191716210.1186/s12964‑019‑0366‑y31186013
    [Google Scholar]
  14. WangL. ZhaoX. DingJ. LiuY. LiuH. ZhengL. ZhaoH. SunZ. LiK. CaiJ. QiaoT. Oridonin attenuates the progression of atherosclerosis by inhibiting NLRP3 and activating Nrf2 in apolipoprotein E-deficient mice.Inflammopharmacology20233141993200510.1007/s10787‑023‑01161‑937155118
    [Google Scholar]
  15. ZhouF. GaoH. ShangL. LiJ. ZhangM. WangS. LiR. YeL. YangS. Oridonin promotes endoplasmic reticulum stress via TP53-repressed TCF4 transactivation in colorectal cancer.J. Exp. Clin. Cancer Res.202342115010.1186/s13046‑023‑02702‑437337284
    [Google Scholar]
  16. ChenM. ShenY. Oridonin represses lung cancer cell proliferation and migration by modulating AFAP1-AS1/IGF2BP1.Cell. Mol. Biol.202470610811310.14715/cmb/2024.70.6.1738836673
    [Google Scholar]
  17. GuiY. ChengJ. ChenZ. Oridonin improves the therapeutic effect of lentinan on lung cancer.Exp. Ther. Med.202122288610.3892/etm.2021.1031834194564
    [Google Scholar]
  18. WangY.Y. LvY.F. LuL. CaiL. Oridonin inhibits mTOR signaling and the growth of lung cancer tumors.Anticancer Drugs201425101192120010.1097/CAD.000000000000015425075795
    [Google Scholar]
  19. LiS. ShiD. ZhangL. YangF. ChengG. Oridonin enhances the radiosensitivity of lung cancer cells by upregulating Bax and downregulating Bcl-2.Exp. Ther. Med.20181664859486410.3892/etm.2018.680330546402
    [Google Scholar]
  20. JiX. QinX. HuangX. WangW. LiH. ZhengC. HuangY. S100A11: A potential carcinogen and prognostic marker that correlates with the immunosuppressive microenvironment in pan-cancer.J. Cancer2023141889810.7150/jca.7801136605485
    [Google Scholar]
  21. WooT. OkudelaK. MitsuiH. TajiriM. RinoY. OhashiK. MasudaM. Up-regulation of S100A11 in lung adenocarcinoma: Its potential relationship with cancer progression.PLoS One20151011e014264210.1371/journal.pone.014264226544866
    [Google Scholar]
  22. ZhangL. ZhuT. MiaoH. LiangB. The calcium binding protein S100A11 and its roles in diseases.Front. Cell Dev. Biol.2021969326210.3389/fcell.2021.69326234179021
    [Google Scholar]
  23. NiH.M. ChaoX. DingW.X. S100A11 overexpression promotes fatty liver diseases via increased autophagy?Cell. Mol. Gastroenterol. Hepatol.202111388588610.1016/j.jcmgh.2020.11.01333290740
    [Google Scholar]
  24. WangH. YinM. YeL. GaoP. MaoX. TianX. XuZ. DaiX. ChengH. S100A11 promotes glioma cell proliferation and predicts grade-correlated unfavorable prognosis.Technol. Cancer Res. Treat.2021201533033821101196110.1177/1533033821101196133902363
    [Google Scholar]
  25. TuY. XieP. DuX. FanL. BaoZ. SunG. zhaoP. ChaoH. LiC. ZengA. PanM. JiJ. S100A11 functions as novel oncogene in glioblastoma via S100A11/ANXA2/NF-κB positive feedback loop.J. Cell. Mol. Med.201923106907691810.1111/jcmm.1457431430050
    [Google Scholar]
  26. CuiY. LiL. LiZ. YinJ. LaneJ. JiJ. JiangW.G. Dual effects of targeting S100A11 on suppressing cellular metastatic properties and sensitizing drug response in gastric cancer.Cancer Cell Int.202121124310.1186/s12935‑021‑01949‑133931048
    [Google Scholar]
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