Small interfering RNA targeting STAT3 enhances antitumor activity of doxorubicin / 药学学报

ABSTRACT

This study is to investigate the effect of small interfering RNA targeting STAT3 (STAT3-siRNA) enhancing antitumor activity of doxorubicin. RT-PCR and Western blotting were used to test the expression of STAT3 mRNA and protein in the HepG2, HeLa and K562/DOX cells and the effect of STAT3-siRNA on the expression of STAT3 mRNA and protein. MTT and Trypan blue assay were performed to determine the inhibitory effect of STAT3-siRNA on HepG2, HeLa and K562/DOX cells and the effect of STAT3-siRNA enhancing antitumor activity of doxorubicin. The effects of STAT3-siRNA on intracellular accumulation of doxorubicin and cell apoptosis were performed by Arrary Scan V(TI)HCS600 High-Contents. The results showed that STAT3 gene, STAT3 and pSTAT3 protein were highly expressed in HepG2, HeLa and K562/DOX cells and STAT3-siRNA decreased the expression of STAT3 mRNA and protein. STAT3-siRNA inhibited the growth of HepG2, HeLa and K562/DOX cells. STAT3-siRNA in combination with doxorubicin decreased by 3.13, 5.22 and 1.74 fold of IC50 of HepG2, HeLa and K562/DOX cells compared with doxorubicin only. Intracellular accumulation of doxorubicin increased by 16.8%, 12.87% and 25.67% respectively in HepG2, HeLa and K562/DOX cells in the presence of STAT3-siRNA. An enhancement of doxorubicin-induced cell apoptosis was observed in HepG2, HeLa and K562/DOX cells treated with STAT3-siRNA. The results suggested that STAT3-siRNA could enhance the antitumor activity of doxorubicin on HepG2, HeLa and K562/DOX cells.