Skip to content
2000
image of Differential Expression and Distribution of Slco4a1 and Slco1b2 in an Internal Environment Disorder-induced Hepatocellular Carcinoma Mouse Model

Abstract

Objective

This study aims to enhance the understanding of underlying mechanisms and potential therapies of the solute carrier organic anion (SLCO) transporter family in internal environment disorder (IED)-induced hepatocellular carcinoma (HCC). This could lead to new therapeutic strategies and offer new directions for the creation of new patents for HCC treatment products.

Methods

The orthotopic transplantation (OT), IED and IED-based OT (IED-OT) mouse models were established. Expression patterns of Slco4a1 and Slco1b2 were determined using reverse transcription-quantitative polymerase chain reaction (RT-qPCR), western blotting (WB) and immunohistochemistry (IHC) in various tissues, including lung, stomach, liver, spleen, kidney, colon, small intestine, HCC tissues and adjacent non-cancerous tissues.

Results

Animals exhibited symptoms, including weight loss, lethargy, chills, dyspnea, altered hair texture, and gastrointestinal disturbances, confirming the successful establishment of the IED model. The analysis demonstrated differential expression and tissue-specific distribution of Slco4a1 and Slco1b2, which are associated with IED-induced changes. These alterations potentially disrupt organ transport functions, thereby promoting the development of HCC. Additionally, they suggest a role in rebalancing the tumor microenvironment and mitigating damage resulting from abnormal substance accumulation.

Conclusions

Changes in SLCO expression and distribution induced by IED may play pivotal roles in the development of HCC. These findings contribute insights that could inform novel therapeutic strategies against HCC.

Loading

Article metrics loading...

/content/journals/pra/10.2174/0115748928351523241204071335
2025-01-03
2025-07-13
Loading full text...

Full text loading...

References

  1. Yan X. Qiu Y. Impact of current staging systems on treatment strategy for HBV-related hepatocellular carcinoma. Cancer Lett. 2016 379 2 220 224 10.1016/j.canlet.2015.08.009 26282785
    [Google Scholar]
  2. Wu Q. Li P. Tao X. Lin N. Mao B. Xie X. A novel super-enhancer-related risk model for predicting prognosis and guiding personalized treatment in hepatocellular carcinoma. BMC Cancer 2024 24 1 1087 10.1186/s12885‑024‑12874‑7 39223584
    [Google Scholar]
  3. Cranford H.M. Jones P.D. Wong R.J. Liu Q. Kobetz E.N. Reis I.M. Koru-Sengul T. Pinheiro P.S. Hepatocellular Carcinoma Etiology Drives Survival Outcomes: A Population-Based Analysis. Cancer Epidemiol. Biomarkers Prev. 2024 OF1 OF10 10.1158/1055‑9965.EPI‑24‑0626 39240221
    [Google Scholar]
  4. Lamarca A. Mendiola M. Barriuso J. Hepatocellular carcinoma: Exploring the impact of ethnicity on molecular biology. Crit. Rev. Oncol. Hematol. 2016 105 65 72 10.1016/j.critrevonc.2016.06.007 27372199
    [Google Scholar]
  5. M ELIZABETH Methods of treating cancer by administration of neohelper PD-1 inhibitors. China patent 117043193, 2023
  6. Tongsen Z. Xuehan L. Shun L. Yan Z. Jiaqi S. Siqi L. Xianjun L. A nano drug loaded particle loaded by macrophages and its preparation method and application. China patent 118045060, 2024
  7. J LI USE OF anti-PVRIG/anti-TIGIT bispecific antibody in treatment of malignant tumors. China patent WO/2024/153182, 2024
  8. Li L. Wang H. Heterogeneity of liver cancer and personalized therapy. Cancer Lett. 2016 379 2 191 197 10.1016/j.canlet.2015.07.018 26213370
    [Google Scholar]
  9. Peng J.X. Wang L.Z. Wang Q.T. Li H.L. Lin L.J. He J.M. Tenofovir versus entecavir on the prognosis of hepatitis B virus-related hepatocellular carcinoma: A reconstructed individual patient data meta-analysis. Front. Pharmacol. 2024 15 1393861 10.3389/fphar.2024.1393861 39239648
    [Google Scholar]
  10. B JIANFENG Computer system for diagnosing, detecting, monitoring and predicting prognosis of HBV (Hepatitis B Virus)-related liver cancer. China patent 202311836446.3, 2023
  11. Chen J.L. Lin X.J. Zhou Q. Shi M. Li S.P. Lao X.M. Association of HBV DNA replication with antiviral treatment outcomes in the patients with early-stage HBV-related hepatocellular carcinoma undergoing curative resection. Chin. J. Cancer 2016 35 1 28 10.1186/s40880‑016‑0089‑z 26992891
    [Google Scholar]
  12. Chin Y.T. Wu M.H. Shih H.Y. Tsai C.W. Pei J.S. Ke T.W. Wang Y.C. Hung Y.C. Chen J.C. Bau D.T. Chang W.S. Diagnostic impacts of aldehyde dehydrogenase 2 genetic variants on hepatocellular carcinoma susceptibility. Cancer Diagn. Progn. 2024 4 5 579 585 10.21873/cdp.10366 39238625
    [Google Scholar]
  13. Mazzanti R. Arena U. Tassi R. Hepatocellular carcinoma: Where are we? World J. Exp. Med. 2016 6 1 21 36 10.5493/wjem.v6.i1.21 26929917
    [Google Scholar]
  14. Abe H. Aida Y. Ishiguro H. Yoshizawa K. Miyazaki T. Itagaki M. Sutoh S. Aizawa Y. Alcohol, postprandial plasma glucose, and prognosis of hepatocellular carcinoma. World J. Gastroenterol. 2013 19 1 78 85 10.3748/wjg.v19.i1.78 23326166
    [Google Scholar]
  15. Hlady R.A. Tiedemann R.L. Puszyk W. Zendejas I. Roberts L.R. Choi J.H. Liu C. Robertson K.D. Epigenetic signatures of alcohol abuse and hepatitis infection during human hepatocarcinogenesis. Oncotarget 2014 5 19 9425 9443 10.18632/oncotarget.2444 25294808
    [Google Scholar]
  16. Zhou J. Hou W. Zhong H. Liu D. Lung microbiota: Implications and interactions in chronic pulmonary diseases. Front. Cell. Infect. Microbiol. 2024 14 1401448 10.3389/fcimb.2024.1401448 39233908
    [Google Scholar]
  17. Bhattacharjee P. Banerjee M. Giri A.K. Role of genomic instability in arsenic-induced carcinogenicity. A review. Environ. Int. 2013 53 29 40 10.1016/j.envint.2012.12.004 23314041
    [Google Scholar]
  18. Gajjar K. Martin-Hirsch P.L. Martin F.L. CYP1B1 and hormone-induced cancer. Cancer Lett. 2012 324 1 13 30 10.1016/j.canlet.2012.04.021 22561558
    [Google Scholar]
  19. Nguyen-Ngoc K.V. Cheung K.J. Brenot A. Shamir E.R. Gray R.S. Hines W.C. Yaswen P. Werb Z. Ewald A.J. ECM microenvironment regulates collective migration and local dissemination in normal and malignant mammary epithelium. Proc. Natl. Acad. Sci. USA 2012 109 39 E2595 E2604 10.1073/pnas.1212834109 22923691
    [Google Scholar]
  20. de la Cruz-Merino L. Henao Carrasco F. Vicente Baz D. Nogales Fernández E. Reina Zoilo J.J. Codes Manuel de Villena M. Pulido E.G. Immune microenvironment in colorectal cancer: A new hallmark to change old paradigms. Clin. Dev. Immunol. 2011 2011 1 9 10.1155/2011/174149 22162710
    [Google Scholar]
  21. Zamarron B.F. Chen W. Dual roles of immune cells and their factors in cancer development and progression. Int. J. Biol. Sci. 2011 7 5 651 658 10.7150/ijbs.7.651 21647333
    [Google Scholar]
  22. Mahadevan D. Von Hoff D.D. Tumor-stroma interactions in pancreatic ductal adenocarcinoma. Mol. Cancer Ther. 2007 6 4 1186 1197 10.1158/1535‑7163.MCT‑06‑0686 17406031
    [Google Scholar]
  23. Vasuri F. Golfieri R. Fiorentino M. Capizzi E. Renzulli M. Pinna A.D. Grigioni W.F. D’Errico-Grigioni A. OATP 1B1/1B3 expression in hepatocellular carcinomas treated with orthotopic liver transplantation. Virchows Arch. 2011 459 2 141 146 10.1007/s00428‑011‑1099‑5 21691816
    [Google Scholar]
  24. Vavricka S.R. Jung D. Fried M. Grützner U. Meier P.J. Kullak-Ublick G.A. The human organic anion transporting polypeptide 8 (SLCO1B3) gene is transcriptionally repressed by hepatocyte nuclear factor 3β in hepatocellular carcinoma. J. Hepatol. 2004 40 2 212 218 10.1016/j.jhep.2003.10.008 14739090
    [Google Scholar]
  25. Wang Y. Wang Y. Fang Y. Jiang H. Yu L. Hu H. Zeng S. SND1 regulates organic anion transporter 2 protein expression and sensitivity of hepatocellular carcinoma cells to 5-fluorouracil. Drug Metab. Dispos. 2024 52 9 997 1008 10.1124/dmd.124.001757 38960734
    [Google Scholar]
  26. Wlcek K. Svoboda M. Riha J. Zakaria S. Olszewski U. Dvorak Z. Sellner F. Ellinger I. Jäger W. Thalhammer T. The analysis of organic anion transporting polypeptide (OATP) mRNA and protein patterns in primary and metastatic liver cancer. Cancer Biol. Ther. 2011 11 9 801 811 10.4161/cbt.11.9.15176 21383546
    [Google Scholar]
  27. Shihua X. Haoxuan L. Ting X. Shijun Z. Effect of internal environment of spleen deficiency on expressions of Oatp2a1, Oatp2b1, Oatp4a1 and Oatp1b2 in gastric tissues of mice with induced liver cancer. Zhonghua Zhongyiyao Xuekan 2019 37 10 2358 2362
    [Google Scholar]
  28. L Hao⁃xuan The effect of transmembrane renal organic anion transport on drug⁃induced hepatocellular carcinoma mice model with internal environment disorder. Anat Res 2020 42 2 150 156
    [Google Scholar]
  29. Minor T.R. Hanff T.C. Adenosine signaling in reserpine-induced depression in rats. Behav. Brain Res. 2015 286 184 191 10.1016/j.bbr.2015.02.032 25721738
    [Google Scholar]
  30. Leão A.H.F.F. Sarmento-Silva A.J. Santos J.R. Ribeiro A.M. Silva R.H. Molecular, neurochemical, and behavioral hallmarks of reserpine as a model for parkinson’s disease: New perspectives to a long‐standing model. Brain Pathol. 2015 25 4 377 390 10.1111/bpa.12253 25726735
    [Google Scholar]
  31. Neisewander J.L. Castañeda E. Davis D.A. Dose-dependent differences in the development of reserpine-induced oral dyskinesia in rats: Support for a model of tardive dyskinesia. Psychopharmacology 1994 116 1 79 84 10.1007/BF02244874 7862934
    [Google Scholar]
  32. Nur S. Adams C.E. Chlorpromazine versus reserpine for schizophrenia. Cochrane Database Syst. Rev. 2016 4 4 CD012122 27124109
    [Google Scholar]
  33. Blasco-Serra A. Escrihuela-Vidal F. González-Soler E.M. Martínez-Expósito F. Blasco-Ausina M.C. Martínez-Bellver S. Cervera-Ferri A. Teruel-Martí V. Valverde-Navarro A.A. Depressive-like symptoms in a reserpine-induced model of fibromyalgia in rats. Physiol. Behav. 2015 151 456 462 10.1016/j.physbeh.2015.07.033 26222614
    [Google Scholar]
  34. Okano H. Masuda H. Ohkubo C. Effects of 25 mT static magnetic field on blood pressure in reserpine‐induced hypotensive Wistar‐Kyoto rats. Bioelectromagnetics 2005 26 1 36 48 10.1002/bem.20052 15605399
    [Google Scholar]
  35. Rao Q. You A. Guo Z. Zuo B. Gao X. Zhang T. Du Z. Wu C. Yin H. Intrahepatic tissue implantation represents a favorable approach for establishing orthotopic transplantation hepatocellular carcinoma mouse models. PLoS One 2016 11 1 e0148263 10.1371/journal.pone.0148263 26824903
    [Google Scholar]
  36. Kang H. Sample size determination and power analysis using the G*Power software. J. Educ. Eval. Health Prof. 2021 18 17 10.3352/jeehp.2021.18.17 34325496
    [Google Scholar]
  37. Gao X.L. Guo W.F. Li R.L. Chen W.W. Effects of Sijunzi Decoction on urine’s xylose excretion rate and ATP in mucosa of spleen deficiency rats. Zhong Yao Cai 2009 32 8 1242 1245 19960947
    [Google Scholar]
  38. Ren P Huang X Zhang L Effect of Sijunzi decoction on gastric emptying rate in rat model of spleen deficiency syndrome. Chin. J. Integr. Tradit. Western Med. 2000 205 96 98
    [Google Scholar]
  39. Zhao N. Zhang W. Guo Y. Jia H. Zha Q. Liu Z. Xu S. Lu A. Effects on neuroendocrinoimmune network of Lizhong Pill in the reserpine induced rats with spleen deficiency in traditional Chinese medicine. J. Ethnopharmacol. 2011 133 2 454 459 10.1016/j.jep.2010.10.016 20951788
    [Google Scholar]
  40. Sun B. Meng J. Xiang T. Zhang L. Deng L. Chen Y. Luo H. Yang Z. Chen Z. Zhang S. Effect of the herbal formulation Jianpijiedu on the TCRVβCDR3 repertoire in rats with hepatocellular carcinoma and subjected to food restriction combined with laxative. Exp. Ther. Med. 2016 11 3 818 826 10.3892/etm.2015.2955 26997998
    [Google Scholar]
  41. Yang J.D. Nakamura I. Roberts L.R. The tumor microenvironment in hepatocellular carcinoma: Current status and therapeutic targets. Semin. Cancer Biol. 2011 21 1 35 43 10.1016/j.semcancer.2010.10.007 20946957
    [Google Scholar]
  42. Yoneda T. Hiraga T. Crosstalk between cancer cells and bone microenvironment in bone metastasis. Biochem. Biophys. Res. Commun. 2005 328 3 679 687 10.1016/j.bbrc.2004.11.070 15694401
    [Google Scholar]
  43. Galasso L. Cerrito L. Maccauro V. Termite F. Mignini I. Esposto G. Borriello R. Ainora M.E. Gasbarrini A. Zocco M.A. Inflammatory response in the pathogenesis and treatment of hepatocellular carcinoma: A double-edged weapon. Int. J. Mol. Sci. 2024 25 13 7191 10.3390/ijms25137191 39000296
    [Google Scholar]
  44. Mikkaichi T. Suzuki T. Tanemoto M. Ito S. Abe T. The organic anion transporter (OATP) family. Drug Metab. Pharmacokinet. 2004 19 3 171 179 10.2133/dmpk.19.171 15499184
    [Google Scholar]
  45. Wu Z. Yuan J. Li K. Wang X. Zhang Z. Hong M. The induction of drug uptake transporter OATP1A2 by radiation is mediated by non-receptor tyrosine kinase YES-1. Drug Metab. Dispos. 2024 10.1124/dmd.124.001755
    [Google Scholar]
/content/journals/pra/10.2174/0115748928351523241204071335
Loading
/content/journals/pra/10.2174/0115748928351523241204071335
Loading

Data & Media loading...

This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error
Please enter a valid_number test