槐定碱通过PI3K/Akt/mTOR信号通路诱导自噬抑制胰腺癌细胞增殖

目的 探讨槐定碱对胰腺癌细胞增殖及自噬的影响，并分析其机制。方法 MTT法分析Sw1990细胞增殖， MDC染色法检测细胞自噬水平，western blot检测细胞自噬相关蛋白、PI3K/Akt/mTOR信号通路相关蛋白表达水平，运用自噬抑制剂（3 - MA）研究自噬对细胞增殖的影响；裸鼠成瘤实验检测体内胰腺癌细胞增殖情况，并分析瘤组织中LC3 II、p - mTOR蛋白水平。结果 槐定碱抑制胰腺癌Sw1990细胞的增长，促进自噬小泡的形成，上调LC3 II/ LC3 I、Beclin - 1水平，下调p - PI3K、p - AKT、p - mTOR水平（P＜0.05）；与槐定碱40 μmol/L组比较，槐定碱40 μmol/L + 3 - MA 5 μmol/L组细胞抑制率升高，LC3 II/ LC3 I降低，p - mTOR蛋白水平升高（P＜0.05）； 40 mg/kg槐定碱下调裸鼠瘤体体积、瘤体质量，上调LC3 II/ LC3 I水平，下调p - mTOR蛋白水平（P＜0.05）。结论 槐定碱能抑制Sw1990细胞增殖，与调控PI3K/Akt/mTOR信号通路影响自噬有关。

Sophoridine induces autophagy and inhibits the proliferation of pancreatic cancer cells through PI3K/Akt/mTOR signaling pathway

To investigate the effect of sophoridine on the proliferation and autophagy of pancreatic cancer cells and analyze its mechanism. Methods The inhibitory effect of pancreatic cancer cells was analyzed by MTT method. MDC staining method was used to detect the autophagy of Sw1990 cells, and Western blot to detect the autophagy-related proteins and PI3K/Akt/mTOR signaling pathway-related proteins. Autophagy inhibitor(3-MA) was used to study the effect of autophagy on cell proliferation. Nude mice tumorigenesis test was performed to detect the proliferation of pancreatic cancer Sw1990 cells in vivo, and the levels of LC3 Ⅱ and p-mTOR in tumor tissues were analyzed. Results Sophoridine could significantly inhibit the growth of pancreatic cancer Sw1990 cells, stimulate the formation of autophagy vesicles, upregulate LC3 Ⅱ/LC3 Ⅰ and Beclin-1, and downregulate p-PI3K, p-AKT, and p-mTOR significantly(P <0.05). Compared with sophoridine 40 μM group, the cell inhibition rate was significantly increased, LC3 Ⅱ/LC3 Ⅰ decreased significantly, and the p-mTOR protein level increased significantly in sophoridine 40 μM+3-MA 5 μM group(P<0.05). 40 mg/kg sophoridine could significantly reduce the tumor volume and tumor mass of nude mice, increase the LC3 Ⅱ/LC3 Ⅰ levels significantly, and decrease the p-mTOR protein levels significantly(P<0.05). Conclusion Sophoridine can inhibit the proliferation of Sw1990 cells, which may be related to the regulation of PI3K/Akt/mTOR signaling pathway and its effect on autophagy.