STAT3磷酸化抑制剂隐丹参酮提高5-FU诱导的结直肠癌细胞凋亡

Signal transducer and activator of transcription 3 inhibitor cryptotanshinone promotes colorectal cancer cells apoptosis induced by 5-FU

目的探究结直肠癌细胞中利用信号转导蛋白和转录激活因子3(STAT3)磷酸化抑制剂隐丹参酮(CTS)抑制STAT3 705位点磷酸化对5-氟尿嘧啶(5-FU)效果的影响。方法采用Western印迹法检测5株结直肠癌细胞中STAT3的磷酸化水平,挑选磷酸化程度最高的2株细胞进行后续实验研究。采用Western印迹法检测5-FU处理后结直肠癌细胞STAT3磷酸化水平的变化。应用MTT实验评价5-FU与CTS联合处理结直肠癌细胞对细胞活性影响。利用流式细胞仪检测5-FU与CTS联合处理细胞后对细胞凋亡的影响,同时利用Western印迹法检测抗凋亡蛋白Bcl2的变化情况。结果 5-FU能够降低结直肠癌细胞STAT3 705位点磷酸化水平,利用CTS抑制STAT3磷酸化极大的增强了5-FU的作用效果,降低了结直肠癌细胞活性,促进了细胞凋亡。同时进一步机制研究表明CTS与5-FU联合作用降低了Bcl2蛋白水平。结论结直肠癌细胞中,利用STAT3磷酸化抑制剂CTS抑制STAT3磷酸化水平能够明显提高5-FU的作用效果。

Objective To explore the effect on the function of 5-fluorouracil（5-FU）in colorectal cancer cells when the level of phosphorylation at Tyr705 of signal transducer and activator of transcription 3（STAT3）is inhibited by STAT3 inhibitor cryptotanshinone（CTS）. Methods The level of phosphorylation of STAT3 was detected in 5 colorectal cancer cells by Western blot,and the highest two were selected for subsequent research. The colorectal cancer cells were treated by 5-FU and the level of phosphorylation of STAT3 was detected by Western blot. MTT Assay was used to detect the cell activity treated with 5-FU or 5-FU with CTS. Fluorescence-activated cell sorting（FACS）was used to detect the cell apoptosis induced by 5-FU or 5-FU with CTS,meanwhile the level of anti- apoptosis protein Bcl2 was detected by Western blot. Results 5- FU could reduce the level of phosphorylation at Tyr705 of STAT3 in colorectal cancer cells. Inhibition of the phosphorylation of STAT3 by CTS significantly enhanced the function of 5-FU,including reducing the activity of colorectal cancer cells and promoting cell apoptosis. Further exploration of the mechanism of 5-FU with CTS indicated that the level of Bcl2 was decreased. Conclusion The inhibition of the level of phosphorylation of STAT3 by inhibitor CTS promotes the effect of 5-FU in colorectal cancer cells.