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转染pro-GRP表达载体通过JAK1/STAT3信号通路诱导小细胞肺癌细胞H446凋亡的实验研究
作者:时政1  张正伟2 
单位:1. 成都大学 医学院, 四川 成都 610106;
2. 成都市第五人民医院 肿瘤科, 四川 成都 611130
关键词:小细胞肺癌 胃泌素释放肽前体 Janus激酶1/信号转导子和转录激活子3 凋亡 增殖 
分类号:R734.2
出版年·卷·期(页码):2019·38·第四期(661-666)
摘要:

目的:探讨胃泌素释放肽前体(pro-GRP)对小细胞肺癌细胞H446增殖的影响及其分子机制。方法:培养小细胞肺癌细胞H446,将其分为阴性对照组(转染空白质粒)、pro-GRP过表达组(转染pro-GRP表达质粒)、pro-GRP过表达+AG490组(转染pro-GRP表达质粒并用STAT3抑制剂AG490处理)。处理24 h后测定细胞的增殖活力以及线粒体凋亡基因Bcl-2、Bax、Caspase-3和JAK1/STAT3信号通路分子的表达量。结果:pro-GRP、p-JAK1、p-STAT3的蛋白表达量pro-GRP过表达组高于阴性对照组,差异均有统计学意义(P<0.05)。细胞活力检测450 nm处的吸光度、Bcl-2的蛋白表达量pro-GRP过表达组高于阴性对照组,差异均有统计学意义(P<0.05);Bax、Caspase-3的蛋白表达量pro-GRP过表达组低于阴性对照组,差异均有统计学意义(P<0.05)。细胞活力检测450 nm处的吸光度、Bcl-2的蛋白表达量pro-GRP过表达+AG490组低于pro-GRP过表达组,差异均有统计学意义(P<0.05);Bax、Caspase-3的蛋白表达量pro-GRP过表达+AG490组高于pro-GRP过表达组,差异均有统计学意义(P<0.05)。结论:转染pro-GRP表达载体能够通过JAK1/STAT3信号通路抑制线粒体途径细胞凋亡并促进小细胞肺癌细胞H446的增殖。

Objective: To investigate the effect of pro-GRP on the proliferation of small cell lung cancer cell H446 and its molecular mechanism. Methods: Small cell lung cancer cells H446 were cultured and divided into negative control group (transfected with blank plasmid), pro-GRP overexpression group (transfected with pro-GRP expression plasmid), pro-GRP overexpression+AG490 group (transfected with pro-GRP expression plasmid and STAT3 inhibitor AG490). After 24 hours of treatment, the cell proliferation activity and the expression of mitochondrial apoptotic genes Bcl-2, Bax, Caspase-3 and JAK1/STAT3 signaling pathway were determined. Results: The protein expression levels of pro-GRP, p-JAK1 and p-STAT3 in the pro-GRP overexpression group were significantly higher than those in the negative control group (all P<0.05). The light absorption value and the protein expression level of Bcl-2 in the pro-GRP overexpression group at 450 nm were higher than those in the negative control group, and the protein expression levels of Bax and Caspase-3 were significantly lower than those in the negative control group (all P<0.05). The light absorption value and the protein expression level of Bcl-2 in the pro-GRP overexpression+AG490 group at 450 nm were lower than those in the pro-GRP overexpression group (all P<0.05). The protein expression levels of Bax and Caspase-3 in the pro-GRP overexpression +AG490 group were significantly higher than those in the pro-GRP overexpression group (P<0.05).Conclusion: Transfection of pro-GRP expression vector can inhibit mitochondrial pathway apoptosis and promote the proliferation of small cell lung cancer cell line H446 through JAK1/STAT3 signaling pathway.

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