吉林大学学报(医学版) ›› 2023, Vol. 49 ›› Issue (2): 332-340.doi: 10.13481/j.1671-587X.20230209

• 基础研究 • 上一篇    下一篇

姜黄素通过下调PI3K/Akt/mTOR信号通路蛋白表达对胃癌MGC-803细胞增殖和侵袭的抑制作用

孙逸飞1,2,李迪诺2,王玉彬2()   

  1. 1.锦州医科大学研究生院,辽宁 锦州 121000
    2.锦州医科大学附属第一医院普外胃肠科,辽宁 锦州 121000
  • 收稿日期:2022-04-12 出版日期:2023-03-28 发布日期:2023-04-24
  • 通讯作者: 王玉彬 E-mail:wyb641025@163.com
  • 作者简介:孙逸飞(1996-),男,山东省淄博市人,在读硕士研究生,主要从事胃癌和结直肠癌等普外科相关疾病治疗方面的研究。
  • 基金资助:
    国家卫健委医药卫生科技发展项目(WA2021RW25);辽宁省科技厅自然科学基金项目(20170540334)

Inhibitory effect of curcumin on proliferation and invasion of gastric cancer MGC-803 cells by down-regulating PI3K/Akt/mTOR signaling pathway protein expression

Yifei SUN1,2,Dinuo LI2,Yubin WANG2()   

  1. 1.Graduate School,Jinzhou Medical University,Jinzhou 121000,China
    2.Department of General Surgery and Gastroenterology,First Affiliated Hospital,Jinzhou Medical University,Jinzhou 121000,China
  • Received:2022-04-12 Online:2023-03-28 Published:2023-04-24
  • Contact: Yubin WANG E-mail:wyb641025@163.com

摘要:

目的 观察姜黄素对胃癌MGC-803细胞体内外增殖和侵袭的作用,探讨磷脂酰肌醇3-激酶(PI3K)/蛋白激酶B(Akt)/哺乳动物雷帕霉素靶蛋白(mTOR)信号通路的作用机制。 方法 胃癌MGC-803细胞分为对照组、低剂量(10 μmol·L-1)姜黄素组、中剂量(20 μmol·L-1)姜黄素组和高剂量(40 μmol·L-1)姜黄素组。采用CCK-8法检测各组MGC-803细胞增殖能力,Transwell法检测各组MGC-803细胞侵袭能力,流式细胞术检测各组MGC-803细胞凋亡率。采用MGC-803细胞建立胃癌移植瘤模型,分别使用低剂量(0.5 mg·kg-1)、中剂量(1.0 mg·kg-1)和高剂量(2.0 mg·kg-1)姜黄素处理小鼠,观察姜黄素对各组小鼠肿瘤生长的抑制作用,TUNEL法检测各组小鼠移植瘤组织中肿瘤细胞的凋亡情况,Western blotting法检测各组小鼠移植瘤组织中PI3K/Akt/mTOR信号通路蛋白表达水平。 结果 与对照组比较,不同剂量姜黄素组细胞增殖能力和侵袭细胞数明显降低(P<0.05),细胞凋亡率明显升高(P<0.05);低剂量姜黄素组中的胃癌MGC-803细胞增殖能力和侵袭细胞数明显高于高剂量姜黄素组(P<0.05),细胞凋亡率明显低于高剂量姜黄素组(P<0.05)。与对照组比较,不同剂量姜黄素组小鼠移植瘤体积明显缩小(P<0.05)。对照组小鼠移植瘤的细胞凋亡率较低,中剂量姜黄素组小鼠移植瘤的细胞凋亡率明显高于低剂量姜黄素组(P<0.05),而高剂量姜黄素组小鼠移植瘤的细胞凋亡率明显高于中剂量姜黄素组(P<0.05)。与对照组比较,不同剂量姜黄素组小鼠移植瘤组织中PI3K、磷酸化Akt(p-Akt)和磷酸化mTOR(p-mTOR)蛋白表达水平均明显降低(P<0.05);低剂量姜黄素组小鼠移植瘤组织中PI3K、p-Akt和p-mTOR蛋白表达水平明显低于中剂量姜黄素组(P<0.05);高剂量姜黄素组小鼠移植瘤组织中PI3K、p-Akt和p-mTOR蛋白表达水平明显低于中剂量姜黄素组(P<0.05)。 结论 姜黄素可有效抑制肿瘤生长,降低其侵袭能力,提高肿瘤细胞凋亡率,其机制可能与姜黄素可通过下调PI3K/Akt/mTOR信号通路蛋白表达有关。

关键词: 姜黄素, 胃肿瘤, 磷脂酰肌醇3-激酶, 蛋白激酶B, 哺乳动物雷帕霉素靶蛋白, 细胞增殖, 细胞侵袭, 细胞凋亡

Abstract:

Objective To observe the effect of curcumin on proliferation and invasion of the gastric cancer MGC-803 cells in vitro and in vivo, and to discuss the mechanism of phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt)/mammalian rapamycin target protein (mTOR) signaling pathway. Methods The gastric cancer MGC-803 cells were divided into control group, low dose (10 μmol·L-1) of curcumin group, middle dose (20 μmol·L-1) of curcumin group,and high dose (40 μmol·L-1) of curcumin group. The proliferation abilities of the MGC-803 cells in various groups were detected by CCK-8 method;the invasion abilities of the MGC-803 cells in various groups were detected by Transwell method;the apoptotic rates of the MGC-803 cells were detected by flow cytometry. The MGC-803 cells were used to establish the gastric cancer transplanted tumor model and the mice were treated with low(0.5 mg·kg-1), middle (1.0 mg·kg-1),and high (2.0 mg·kg-1) doses of curcumin, and the inhibitory effect of curcumin on the tumor growth of the mice in various groups was observed. TUNEL method was used to detect the apoptosis of the tumor cells in transplanted tumor tissue of the mice in various groups;the expression levels of PI3K-Akt-mTOR signaling pathway proteins in transplacted tumor tissue of the mice in various groups were detected by Western blotting ththod. Results Compared with control group, the proliferation abilities and number of invasion cells in different doses of curcumin groups were significantly decreased (P<0.05), and the apoptotic rates were significantly increased (P<0.05); the cell proliferation ability and the number of invasion cells in low dose of curcumin group were significantly higher than those in high dose of curcumin group (P<0.05), and the apoptotic rate was significantly lower than that in high dose of curcumin group (P<0.05).Compared with control group, the volumes of transplanted tumor of the mice in different doses of curcumin groups were significantly decreased (P<0.05).The apoptotic rate of the cells in transplanted tumor tissue of the mice in control group was low, and the apoptotic rate of the cells in transplated tumor tissue of the mice in middle dose of curcumin group was significantly higher than that in low dose of curcumin group (P<0.05), while the apoptotic rate of the cells in transplated tumor tissue of the mice in high dose of curcumin group was significantly higher than that in middle dose of curcumin group (P<0.05). Compared with control group, the proteins expression levels of PI3K, phosphorylated Akt(p-Akt) and phosphorylated mTOR(p-mTOR) in transplanted tumor tissue of the mice in different doses of curcumin groups were significantly decreased (P<0.05);the expression levels of PI3K, p-Akt, and p-mTOR proteins in transplanted tumor tissue of the mice in low dose of curcumin group were significantly lower than those in middle dose of curcumin group (P<0.05); the expression levels of PI3K, p-Akt, and p-mTOR proteins in transplanted tumor tissue of the mice in high dose of curcumin group were significantly lower than those in middle dose of curcumin group (P<0.05). Conclusion Curcumin can effectively inhibit the proliferation of tumor, decrease the invasion ability, and increase the apoptotic rate of the tumor cells;its mechanism may be related to down-regulation of expressions of PI3K/Akt/mTOR signaling pathway proteins.

Key words: Curcumin, Stomach neoplasm, Phosphatidylinositol 3-kinase, Protein kinase B, Mammalian target protein of rapamycin, Cell proliferation, Cell invasion, Apoptosis

中图分类号: 

  • R735.2