异甘草素通过抑制PI3K/PKB通路降低胃癌细胞的顺铂耐药性  

Isoliquiritigenin reduces cisplatin resistance of gastric cancer cells by inhibiting PI3K/PKB pathway

作　　者：姜蕾[1] 刘大宁[2] JIANG Lei;LIU Daning(Department of Laboratory,Puyang Oilfield General Hospital,Puyang,Henan,China,457001;Department of Laboratory,Puyang People's Hospital,Puyang,Henan,China,457000)

机构地区：[1]濮阳市油田总医院检验科,河南濮阳457001 [2]濮阳市人民医院检验科,河南濮阳457000

出　　处：《分子诊断与治疗杂志》2022年第7期1094-1098,1103,共6页Journal of Molecular Diagnostics and Therapy

基　　金：河南省科技攻关计划项目(172102210025)。

摘　　要：目的 探讨异甘草素(ISL)对胃癌细胞顺铂(DDP)耐药的作用及其对磷脂酰肌醇3激酶(PI3K)/蛋白激酶B(PKB)通路的调控作用。方法 胃癌细胞系SGC-7901建立DDP耐药细胞模型SGC-7901/DDP,MTT法检测细胞活力筛选出ISL、DDP合适作用浓度,检测ISL对SGC-7901/DDP顺铂敏感性的影响以及ISL与DDP联合处理协同作用。SGC-7901/DDP细胞分对照组、DDP组、ISL+DDP组、胰岛素样生长因子1(IGF-1)组(PI3K/PKB激动剂)。流式细胞术检测细胞凋亡率,划痕实验和Transwell侵袭实验检测各组细胞迁移、侵袭能力,Western Blot检测细胞PI3K/PKB通路相关蛋白表达。裸鼠移植瘤模型检测ISL与DDP对体内移植瘤生长的影响。结果 DDP和ISL均以浓度依赖方式降低SGC-7901和SGC-7901/DDP细胞的存活率,20μmol/L浓度ISL可增强DDP对SGC-7901/DDP细胞活力的抑制作用,且ISL与DDP具协同作用,10μmol/L DDP与20μmol/L ISL联合协同作用最优。与DDP组相比,ISL+DDP组胃癌细胞SGC-7901的增殖、迁移与侵袭显著降低,SGC-7901凋亡明显增加(P<0.05)。ISL+DDP组细胞p-PI3K/PI3K、p-PKB/PKB、磷酸化-雷帕霉素靶蛋白(p-mTOR)/mTOR的比值显著低于DDP组(P<0.05)。且IGF-1可明显减弱ISL对DDP耐药胃癌细胞SGC-7901增殖、迁移和侵袭的抑制作用。ISL与DDP联合给药能明显抑制裸鼠移植瘤的生长,而IGF-1明显逆转ISL与DDP联合给药对裸鼠移植瘤生长的抑制作用。结论 ISL可改善胃癌细胞SGC-7901对DDP耐药性,且ISL介导DDP敏感性增强可能与促进细胞凋亡及抑制PI3K/PKB通路有关。Objective To investigate the effect of Isoliquiritigenin(ISL)on the resistance of gastric cancer cells to cisplatin(DDP)and its regulation on phosphatidylinositol 3-kinase(PI3K)/protein kinase B(PKB)pathway. Methods The gastric cancer cell line SGC-7901 was used to establish a DDP-resistant cell model SGC-7901/DDP. MTT assay was used to detect cell viability to screen the appropriate concentration of ISL and DDP,and to detect the effect of ISL on the sensitivity of SGC-7901/DDP to cisplatin and the synergistic effect of ISL and DDP combined treatment. SGC-7901/DDP cells were divided into the control group,the DDP group,the ISL+DDP group,the insulin-like growth factor 1(IGF-1)group(PI3K/PKB agonist).Flow cytometry was used to detect the apoptosis rate,scratch assay and Transwell invasion assay were used to detect the cell migration and invasion abilities of cells in each group. Western Blot was used to detect the expression of PI3K/PKB pathway-related proteins in cells. Nude mouse xenograft model was used to detect the effects of ISL and DDP on the growth of xenografts in vivo. Results Both DDP and ISL reduced the survival rates of SGC-7901 and SGC-7901/DDP cells in a concentration-dependent manner. ISL at a concentration of 20μmol/L could enhance the inhibitory effect of DDP on the viability of SGC-7901/DDP cells. The synergistic effect of 10 μmol/L of DDP combined with 20 μmol/L of ISL was the best. Compared with the DDP group,the proliferation,migration and invasion of gastric cancer cells SGC-7901 in the ISL+DDP group were significantly decreased,and the apoptosis of SGC-7901 was significantly increased(P<0.05). The ratios of p-PI3K/PI3K,p-PKB/PKB,and phosphorylated-mammalian target of rapamycin(p-m TOR)/m TOR in the ISL+DDP group were significantly lower than those in the DDP group(P<0.05). And IGF-1 could significantly reduce the inhibitory effects of ISL and DDP on the proliferation,migration and invasion of SGC-7901/DDP cells.The combined administration of ISL and DDP could significantly inhibit the gro

关 键 词：异甘草素 胃癌 顺铂 耐药性 磷脂酰肌醇3激酶/蛋白激酶B 

分 类 号：R285[医药卫生—中药学]