miR-205 Reverses MDR-1 Mediated Doxorubicin Resistance via PTEN in Human Liver Cancer HepG2 Cells

• Published in: Cell journal (Yakhteh) Vol. 24; no. 3; pp. 112 - 119
• Main Authors: Li, Mei, Li, Z Hubin, Song, Juanrong, Li, Xu, Zhai, Pengtao, Mu, Xudong, Qiu, Fakai, Yao, Le
• Format: Journal Article
• Language: English
• Published: Iran Royan Institute of Iran 01-03-2022; Royan Institute; Royan Institute (ACECR), Tehran
• Subjects: 1-Phosphatidylinositol 3-kinase; AKT protein; Apoptosis; Biomarkers; Cancer; Cell proliferation; Cell viability; Chemotherapy; Doxorubicin; Drug resistance; Efflux; Flow cytometry; Gene expression; Glycoproteins; Hepatocytes; Liver; Liver cancer; MAP kinase; mir-205; Multidrug resistance; Original; P-Glycoprotein; Polymerase chain reaction; pten; PTEN protein; Reverse transcription; Rhodamine; Transfection; PTEN; Liver Cancer; P-Glycoprotein; miR-205; Drug Resistance
• ISSN: 2228-5806; 2228-5814
• DOI: 10.22074/cellj.2022.7231

The aim of the recent study was to investigate the effects of
on reversing Doxorubicin (DOX) resistance, as chemotherapeutic agents through up-regulation of
in human liver cancer HepG2 cells.
In this experimental study, the drug resistance in liver cancer cells via drug efflux inhibition and enhancing apoptosis by the regulation of
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
transfection in HepG2 and HepG2/DOX cells. Activity of P-gp on drug efflux was measured by the Rhodamine 123 (Rho-123) assay.
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.
overexpression considerably inhibited the HepG2/DOX cells viability (P<0.05). qRT-PCR results revealed that
is a pivotal regulator in PI3K/Akt/P-gp axis. Overexpression
resulted in up-regulation
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 (
) almost abolished the effect of
overexpression (P<0.05). Finally, we found that
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.
These findings may introduce
as a predictive biomarker and a potential treatment target for liver cancer therapy during MDR.