王天晓, 王颖莹, 张中庆. STAT3小分子干扰RNA增强多柔比星的抗肿瘤活性J. 药学学报, 2013,48(1): 52-58.
引用本文: 王天晓, 王颖莹, 张中庆. STAT3小分子干扰RNA增强多柔比星的抗肿瘤活性J. 药学学报, 2013,48(1): 52-58.
shu
WANG Tian-xiao, WANG Ying-ying, ZHANG Zhong-qing. Small interfering RNA targeting STAT3 enhances antitumor activity of doxorubicinJ. 药学学报, 2013,48(1): 52-58.
Citation: WANG Tian-xiao, WANG Ying-ying, ZHANG Zhong-qing. Small interfering RNA targeting STAT3 enhances antitumor activity of doxorubicinJ. 药学学报, 2013,48(1): 52-58.
shu

STAT3小分子干扰RNA增强多柔比星的抗肿瘤活性

Small interfering RNA targeting STAT3 enhances antitumor activity of doxorubicin

    摘要
  • 摘要:

    探讨靶向STAT3的小分子干扰RNA (STAT3-siRNA) 对多柔比星 (doxorubicin, DOX) 的抗肿瘤活性的影响。通过RT-PCR及Western blotting检测STAT3在HepG2、HeLa和K562/DOX细胞中的表达水平以及小分子干扰RNA对STAT3表达的影响。采用MTT法和台盼蓝染色法, 检测STAT3-siRNA对肿瘤细胞的抑制作用及其对DOX抗肿瘤活性的影响。应用高内涵活细胞成像系统检测STAT3-siRNA对细胞内DOX蓄积量以及细胞凋亡的影响。结果显示, STAT3在HepG2、HeLa和K562/DOX细胞中均有高表达, STAT3-siRNA明显下调STAT3 mRNA及STAT3蛋白的表达。STAT3-siRNA可抑制HepG2、HeLa和K562/DOX细胞的生长, STAT3-siRNA与DOX联合应用后对3种细胞的IC50分别降低了3.13倍、5.22倍和1.74倍 (与DOX单独应用比较)。STAT3-siRNA使HepG2、HeLa及K562/DOX细胞内DOX的蓄积量分别增加16.8%、12.87% 和25.67%, 同时明显促进了DOX诱导的细胞凋亡。结果表明, STAT3-siRNA可明显增强DOX的抗肿瘤活性。

     

    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 VTIHCS600 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.

     

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