DH-332促进TRIM40的表达及其通过ERK信号通路重塑代谢抑制胃癌细胞增殖迁移  

DH-332 promotes the expression of TRIM40 and inhibits the proliferation and migration of gastric cancer cells by remodeling metabolism through ERK signaling pathway

作　　者：谭希 李南 李瑞林 苏阳 雷丽霞 张洪亮[1] TAN Xi;LI Nan;LI Rui-lin;SU Yang;LEI Li-xia;ZHANG Hong-liang(The Fourth Clinical College of Xinjiang Medical University,Urumqi,Xinjiang 830000,China)

机构地区：[1]新疆医科大学第四临床医学院,新疆乌鲁木齐830000

出　　处：《解剖学研究》2023年第2期120-126,共7页Anatomy Research

基　　金：新疆维吾尔自治区自然科学基金(2021D01C232)。

摘　　要：目的 探讨DH-332促进TRIM40的表达及其通过ERK信号通路重塑代谢抑制胃癌细胞增殖迁移的机制。方法 选择胃上皮细胞系GES-1、GC细胞系BGC-823作为研究对象,Western blot检测TRIM40的表达情况。构建过表达TRIM40 BGC-823细胞,分为空载组、空载+TRIM40组(TRIM40组)、空载+DH-332组(DH-332组,DH-332浓度为8μmol/mL)、空载+TRIM40+DH-332组(实验组,DH-332浓度为8μmol/mL),采用CCK-8检测细胞的增殖情况;Transwell迁移实验检测细胞的侵袭情况;qRT-PCR法检测TRIM40、GLUT1、PKM2 mRNA水平;Western blot检测TRIM40、GLUT1、PKM2、p-ERK1/2、ERK1/2的表达;ELISA检测乳酸含量、葡萄糖摄取率、ATP浓度。结果 (1)TRIM40在GES-1、BGC-823细胞的表达分别为0.68±0.09和0.24±0.05,差异有统计学意义(P<0.01);实验组的增殖速率明显低于空载组(P<0.01),实验组迁移的细胞数量较空载组相比,显著降低(P<0.01)。(2)实验组GLUT1 mRNA相对表达水平与空载组相比,显著降低(P<0.01),PKM2 mRNA相对表达水平较空载组明显降低(P<0.01)。(3)实验组在蛋白水平上TRIM40表达量显著高于空白对照组(P<0.01),GLUT1、p-ERK1/2蛋白表达量明显低于空载组(P<0.01);ERK1/2蛋白表达量在4组间差异均并无统计学意义(P>0.05)。(4)实验组乳酸含量、葡萄糖摄取率均低于空载组(P<0.01)。结论 DH-332能促进TRIM40表达通过ERK信号通路来抑制胃癌细胞的糖酵解反应,从而抑制胃癌的增殖侵袭及迁移,进而参与胃癌的治疗。Objective To investigate the mechanism of DH-332 promoting the expression of TRIM40 and inhibiting the proliferation and migration of gastric cancer cells by remodeling metabolism through ERK signaling pathway.Methods Gastric epithelial cell line CES-1 and CC cell line BGC-823 were selected as the research objects,and the expression of TRIM40 was detected by Western blot.TRIM40 BCC-823 cells overexpressing TRIM40 were constructed and divided into no-load group,no-load+TRIM40 group(TRIM40 group),no-load+DH-332 group(DH-332 group,DH-332 concentration was 8μmol/mL)and no-load+TRIM40+DH-332 group(experimental group,The concentration of DH-332 was 8μmol/mL),and the cell proliferation was detected by CCK-8.Transwell migration assay was used to detect cell invasion.The mRNA levels of TRIM4O,GLUT1 and PKM2 were detected by qRTPCR.The expressions of TRIM40,GLUT1,PKM2,p-ERK1/2 and ERK1/2 were detected by Western blot.Lactic acid content,glucose uptake rate and ATP concentration were detected by ELISA.Results The expression of TRIM40 was low in gastric cancer cells.The proliferation rate of the experimental group was significantly lower than that of the no-load group(P<0.01),and the number of migrating cells in the experimental group was significantly lower than that of the no-load group(P<0.01).②The relative expression level of CLUT1 mRNA in the experimental group was significantly lower than that in the no-load group(P<0.01),and the relative expression level of PKM2 mRNA was significantly lower than that in the no-load group(P<0.01).The protein expression of TRIM40 in the experimental group was significantly higher than that in the blank control group(P<0.01),and the protein expression of CLUT1 and p-ERK1/2 in the experimental group was significantly lower than that in the blank control group(P<0.01).There was no significant difference in ERK1/2 protein among the four groups.@The lactate content and glucose uptake rate of the experimental group were lower than those of the no-load group(P<0.01).Conclusion DH-332 can p

关 键 词：胃癌 去氢骆驼蓬碱DH-332 三基序蛋白40 糖酵解 ERK信号通路 

分 类 号：R735.2[医药卫生—肿瘤]