miR‐21 inhibition reverses doxorubicin‐resistance and inhibits PC3 human prostate cancer cells proliferation.

Many approaches have been examined to reversing multidrug resistance (MDR), but sub‐optimal target‐based strategies have limited their efficacy. Herein, we investigate microRNA (miR‐21) suppression on the doxorubicin (DOX)‐sensitisation of the DOX‐resistant (PC3/DOX) cell line in prostate cancer (PCa). Expression levels of miR‐21, P‐glycoprotein (P‐gp), MDR‐1 and PTEN evaluated in PC3/DOX cancer cells by qRT‐PCR and western blot analyses. The cytotoxic effects of transfected of miR‐21 were assessed by MTT assay for 72 hr. Rhodamine123 (Rh123) assay was employed to define the activity of P‐gp. Apoptosis was detected by Flow cytometry. As expected, miR‐21 was expressed highly in PC3/DOX cells (p < 0.05). It was shown that miRNA‑21 suppression considerably hindered PC3/DOX cell viability. miR‑21 suppression dramatically downregulated P‐gp expression and activity in DOX‐resistance cells and abolished MDR by an increment of intracellular accumulation of DOX in PC3/DOX cells (p < 0.05). PTEN is a key modulator of the PI3K/Akt/P‐gp cascade, which miR‐21 suppression led to the upregulation of PTEN and sequentially lower‐expression of P‐gp that reversed MDR. Also, miR‐21 repression enhanced the apoptosis rate of PC3/DOX cells. The findings of this paper contribute to the current understanding of the functions of miR‐21 in MDR‐reversing in PCa. [ABSTRACT FROM AUTHOR]