TY - JOUR ID - 251904 TI - MiR-205 Reverses MDR-1 Mediated Doxorubicin Resistance Via PTEN In Human Liver Cancer HepG2 Cells JO - Cell Journal (Yakhteh) JA - CELLJ LA - en SN - 2228-5806 AU - Li, Mei AU - Li, Zhubin AU - Song, Juanrong AU - Li, Xu AU - Zhai, Pengtao AU - Mu, Xudong AU - Qiu, Fakai AU - Yao, Le AD - Department of Minimally Invasive Intervention, Shaanxi Provincial Cancer Hospital, Xi&#039;an, Shaanxi, China AD - Department of Oncology, Shaanxi Provincial Cancer Hospital, Xi&#039;an, Shaanxi, China AD - Department of Infectious Diseases, The First Hospital of Yulin, Yulin, Shaanxi, China Y1 - 2022 PY - 2022 VL - 24 IS - 3 SP - 112 EP - 119 KW - Drug resistance KW - liver cancer KW - miR-205 KW - P-GLYCOPROTEIN KW - PTEN DO - 10.22074/cellj.2022.7231 N2 - Objective: The aim of the recent study was to investigate the effects of miR-205 on reversing Doxorubicin (DOX) resistance, as chemotherapeutic agents through up-regulation of PTEN in human liver cancer HepG2 cells.Materials and Methods: In this experimental study, the drug resistance in liver cancer cells via drug efflux inhibition and enhancing apoptosis by the regulation of PTEN and multi-drug resistance/ P-glycoprotein (MDR/P-gp) expression was revealed. Using 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, effect of DOX on cell proliferation was evaluated after miR-205 transfection in HepG2 and HepG2/DOX cells. Activity of P-gp on drug efflux was measured by the Rhodamine 123 (Rho-123) assay. PTEN mRNA expression levels were measured by quantitative reverse transcription polymerase chain reaction (qRT-PCR) and flow cytometry was used to measure the apoptotic ratio of HepG2/DOX cells.Results: miR-205 overexpression considerably inhibited the HepG2/DOX cells viability (P<0.05). qRT-PCR results revealed that PTEN is a pivotal regulator in PI3K/Akt/P-gp axis. Overexpression miR-205 resulted in up-regulation PTEN and ultimately down-regulation of P-gp. This inhibits drug resistance, proliferation and induces apoptosis in HepG2/DOX cells (P<0.05). Whilst, treatment with 10 μM of special inhibitors, including LY294002 (PI3K) or PD098059 (MAPK), increased Rho 123-associated MFI, treatment with 10 μM of SF1670 (PTEN) almost abolished the effect of miR-205 overexpression (P<0.05). Finally, we found that miR-205 was down-regulated in HepG2/DOX cells, and its overexpression led to enhancing apoptosis with re-sensitization of HepG2/DOX cell lines to DOX through PTEN/PI3K/ Akt/MDR1 pathway.Conclusion: These findings may introduce miR-205 as a predictive biomarker and a potential treatment target for liver cancer therapy during MDR.  UR - https://www.celljournal.org/article_251904.html L1 - https://www.celljournal.org/article_251904_71939c68d65677d922bdd97ea893d3a4.pdf ER -