内质网激动剂调控PI3K/AKT/mTOR通路诱导人小细胞肺癌NCI-H446细胞凋亡

Endoplasmic reticulum agonist induces the apoptosis of NCI-H446 human small cell lung cancer cells via regulation of PI3K/AKT/mTOR pathway

目的检测内质网应激能否通过PI3K/AKT/mTOR通路对人小细胞肺癌NCI-H446细胞凋亡产生作用。方法采用MTT法检测不同浓度衣霉素对人小细胞肺癌NCI-H446的细胞毒性,AnnexinⅤ/PI检测药物作用下人小细胞肺癌NCI-H446细胞凋亡情况,Western Blot检测PI3K/AKT/mTOR通路相关蛋白的表达。结果衣霉素可抑制人小细胞肺癌NCI-H446细胞的活性,且呈时间和浓度依赖性。衣霉素能够激活内质网应激,抑制PI3K/AKT/mTOR信号通路,使PI3K、AKT、mTOR蛋白磷酸化下调,诱导细胞凋亡。结论内质网激动剂能够调控PI3K/AKT/mTOR通路诱导人小细胞肺癌NCI-H446细胞凋亡。

Objective To investigate whether endoplasmic reticulum stress could affect the apoptosis of NCI-H446 human small cell lung cancer cells via PI3K/AKT/mTOR pathway. Method The cytotoxicity of different concentrations of tunicamycin on NCI-H446 human cell lung cancer cells was detected by MTT method, the apoptosis of NCI-H446 induced by tested product was explored by Annexin Ⅴ/PI, and the expression of proteins related to PI3K/AKT/mTOR pathway was analyzed using Western Blot. Result Tunicamycin could inhibit the activity of NCI-H446 human small cell lung cancer cells in a time-and dose-dependent manner. Furthermore, tunicamycin could activate endoplasmic reticulum stress, inhibit PI3K/AKT/mTOR signal pathway, down-regulate the phosphorylation of PI3 K, AKT, mTOR protein, and induce cell apoptosis. Conclusion Endoplasmic reticulum agonist induces the apoptosis of NCI-H446 human small cell lung cancer cells via regulation of PI3K/AKT/mTOR pathway.