Small interfering RNA targeting STAT3 enhances antitumor activity of doxorubicin

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^TIHCS600 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.