Mir-205 Reverses Mdr-1 Mediated Doxorubicin Resistance Via Pten in Human Liver Cancer Hepg2 Cells

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.