丙泊酚通过靶向调控PI3K/AKT/mTOR信号通路体外抑制乳腺癌细胞生长

Study on inhibition of breast cancer cell growth in vitro by propofol throughtargeted regulation of PI3K/AKT/mTOR signaling pathway

目的探讨丙泊酚通过PI3K/AKT/mTOR信号通路对乳腺癌细胞增殖、侵袭及凋亡的影响。方法在体外,丙泊酚10 mg/mL分别与乳腺癌MCF-7和BT474细胞系共孵育分为对照组和丙泊酚组。PI3K过表达质粒经丙泊酚处理后转染MCF-7细胞分为对照组、丙泊酚+PI3K组、PI3K组,分别检测细胞的生存、侵袭及凋亡情况。Western blot检测PI3K/AKT/mTOR信号通路相关蛋白表达水平。在体内构建MCF-7小鼠模型,免疫组化和TUNEL实验用于检测乳腺癌细胞的生长和凋亡情况。结果丙泊酚显著抑制乳腺癌细胞的生长和侵袭能力(P<0.05)。Western blot和细胞凋亡实验结果显示,丙泊酚通过降低Bcl-2和Bcl-w在乳腺癌细胞中的表达水平来诱导细胞凋亡(P<0.05)。丙泊酚降低了乳腺癌细胞中磷酸肌醇3激酶(PI3K)、蛋白激酶B(AKT)和mTOR蛋白表达水平(P<0.05)。对PI3K进行过表达处理后显示,PI3K过表达逆转了丙泊酚对MCF-7细胞的生长和侵袭的抑制作用(P<0.05)。体内实验表明,丙泊酚治疗明显抑制MCF-7小鼠模型中的肿瘤生长,促进了细胞凋亡(P<0.05)。结论丙泊酚通过PI3K/AKT/mTOR信号通路体外抑制乳腺癌细胞的生长和侵袭,促进细胞凋亡。

Objective The purpose of this study was to investigate the role and mechanism of propofol in breast cancer.Methods In vitro,10 mg/mL propofol was co-incubated with Breast cancer MCF-7 and BT474 cells respectively.P13K over-expressed plasmid was transfected with propofol.Cell growth and invasion were measured by cell survival assay and cell invasion assay.Apoptosis assay was used to detect cell apoptosis.Western blot was used to detect the expression of PI3K/AKT/mTOR signaling pathway.In vivo,after MCF-7 mouse model was constructed,immunohistochemistry and TUNEL assay were used to detect the growth and apoptosis of breast tumors.Results Propofol significantly inhibited the growth and invasion of breast cancer cells.Western blot and apoptosis assay showed that propofol induced apoptosis by decreasing the expression levels of B-cell lymphoma(Bcl-2)and Bcl-W in breast cancer cells.Propofol was also observed to reduce the expression levels of phosphoinositol 3 kinase(PI3K),protein kinase B(AKT)and mTOR in breast cancer cells.After P13K over-expression treatment,PI3K over-expression reversed the inhibitory effect of propofol on the growth and invasion of MCF-7 cells.In vivo experiments showed that propofol treatment significantly inhibited tumor growth and promoted apoptosis in MCF-7 mouse models.All the experimental results were statistically significant.Conclusion Propofol inhibits the growth and invasion of breast cancer cells in vitro through PI3K/AKT/mTOR signaling pathway,and promotes apoptosis.