Stat3信号转导通路调控bcl-2成员表达及抑制结肠癌细胞凋亡的机制

Stat3 Signaling Pathway Regulates the Expression of bcl-2 Family Members and Promotes Survival of Human Colon Cancer Cells

目的转录信号转导子与激活子3(Signal transducers and activators of transcription 3,Stat3)通路受细胞因子与生长因子的刺激而活化,参与调节细胞的增殖、分化与凋亡,探讨Stat3反义寡核苷酸诱导结肠癌细胞凋亡的作用机制。方法用阳离子脂质体介导Stat3反义寡核苷酸转染人结肠癌HCT116细胞,MTT法检测细胞增殖状态;流式细胞术检测细胞周期与凋亡;Western blot检测Stat3、磷酸化Stat3及凋亡家族成员bcl-2、bcl-xL、Mcl-1、Caspase-3的表达。结果转染Stat3反义寡核苷酸后HCT116细胞增殖受抑制,凋亡细胞增多,Stat3、p-Stat3与bcl-2家族成员表达水平下降。结论Stat3信号转导通路活性增高可能与结肠癌发生发展有关,阻断Stat3通路可以诱导结肠癌细胞凋亡。

Objective Signal transducer and activator of transcription 3 （Stat3） is activated in response to cytokines and growth factors stimulation, and activation of Stat3 is involved in modulating cell proliferation, differentiation and apoptosis. The purpose of the study was to examine colon cancer cell lines to determine whether Stat3 plays an important role in the process of apoptosis in colon cancer cells. Methods Protein lysates were extracted from colon cancer cells. Human colon cancer cell line HCT116 was transfected with Stat3 antisense oligonucleotide mediated by liposome, MTT assay was used to measure the proliferation, flow cytometry was applied to analyze the cell cycle and apoptosis, the expression of Stat3, p-Stat3, bcl-2, bcl-XL, Mcl-1 and Caspase-3 were measured by western blot. Results Targeting of Stat3 using antisense oligonucleotide directed against the translation site, resulted in apoptosis and downregulation of Stat3, p-Stat3 and bcl-2 family members. Conclusion Constitutive activation of Stat3 is associated with the carcinogenesis of colon cancer cells. Blocking of Stat3 signaling could induce apoptosis of colon cancer cells.