标题：二甲双胍对体外子宫内膜癌细胞COX-2、VEGF和PTEN表达的影响

      作者：贺天虎，邓娟，雷慧，曹云桂    上海市嘉定区妇幼保健院妇科，上海 201821

      卷次： 2023年34卷2期

      【摘要】 目的 探讨二甲双胍在体外对人子宫内膜癌细胞环氧合酶-2 (COX-2)、血管内皮生长因子(VEGF)和张力蛋白同源第10号染色体缺失的磷酸酶(PTEN)蛋白表达的影响。方法 按照二甲双胍干预药物浓度的不同，将细胞实验分为实验组(0.01 mmol/L组，0.1 mmol/L组，1 mmol/L组，10 mmol/L组)和对照组(0 mmol/L组)，分别干预4种人子宫内膜癌 Ishikawa、RL-952、HEC-1A和KLE细胞相同时间后，采用ELISA法检测内膜癌细胞中COX-2和VEGF表达的变化，Western blotting法检测内膜癌细胞中PTEN蛋白的表达情况。结果 Ishikawa和RL-952细胞中4个实验组相对于对照组COX-2和VEGF的表达均随着二甲双胍浓度的增加呈明显下降趋势，差异均有统计学意义(P<0.05)；HEC-1A和KLE细胞中4个实验组相对于对照组COX-2的表达均随着二甲双胍浓度的增加呈下降趋势，但是仅有HEC-1A细胞中 10 mmol/L组差异有统计学意义(P<0.05)，其余实验组差异均无统计学意义(P>0.05)；HEC-1A和KLE细胞中4个实验组相对于对照组VEGF的表达均随着二甲双胍浓度的增加呈明显下降趋势，差异有统计学意义(P<0.05)；Western blotting法检测显示二甲双胍能够促进子宫内膜癌 Ishikawa细胞中PTEN蛋白的表达，差异有统计学意义(P<0.05)，而对RL-952、HEC-1A和KLE细胞中 PTEN蛋白的表达无影响(P>0.05)。结论 二甲双胍可能通过抑制子宫内膜癌细胞中COX-2与VEGF的表达来实现其部分的抗肿瘤作用。
      【关键词】 子宫内膜癌；二甲双胍；环氧合酶-2；血管内皮生长因子；张力蛋白同源第10号染色体缺失的磷酸酶
      【中图分类号】 R737.33 【文献标识码】 A 【文章编号】 1003—6350（2023）02—0171—05

Effects of metformin on expression of cyclooxygenase-2, vascular endothelial growth factor, and phosphatase andtensin homolog deleted on chromosome ten in endometrial carcinoma cells in vitro.
HE Tian-hu, DENG Juan, LEIHui, CAO Yun-gui. Department of Gynaecology, Shanghai Jiading District Maternal and Child Health Hospital, Shanghai201821, CHINA
【Abstract】 Objective To investigate the effects of metformin on the expression of cyclooxygenase-2(COX-2), vascular endothelial growth factor (VEGF) and phosphatase and tensin homolog deleted on chromosome ten(PTEN) in human endometrial carcinoma cells in vitro. Methods According to the different concentrations of metfor-min intervention drugs, the cell experiments were divided into experimental group (0.01 mmol/L group, 0.1 mmol/Lgroup, 1 mmol/L group, 10 mmol/L group) and control group (0 mmol/L group). After the intervention of Ishikawa,RL-952, HEC-1A, and KLE cells of four kinds of human endometrial carcinoma for the same time, and the expressionof COX-2 and VEGF in endometrial cancer cells was detected by ELISA. Expression of PTEN protein in endometrialcancer cells was detected by Western blotting. Results Compared with the control group, the expression levels ofCOX-2 and VEGF in the four experimental groups in the Ishikawa and RL-952 cell groups decreased significantly withthe increase of metformin concentration, and the differences were statistically significant (P<0.05). Compared with thecontrol group, the expression of COX-2 in the 4 experimental groups in the HEC-1A and the KLE cell group decreasedwith the increase of metformin concentration, but only the HEC-1A cell group had a statistically significant difference inthe 10 mmol/L group (P<0.05), and there was no significant difference in other groups (P>0.05). In the HEC-1A andKLE cell, the expression of VEGF in the four experimental groups (compared with the control group) decreased signifi-cantly with the increase of metformin concentration, and the differences were statistically significant (P<0.05). Westernblotting showed that metformin could promote the expression of PTEN protein in endometrial cancer Ishikawa cells, andthe difference was statistically significant (P<0.05), but had no effect on the expression of PTEN in RL-952, HEC-1Aand KLE cells (P>0.05). Conclusion Metformin partially achieves anti-tumor effects by inhibiting the expression ofCOX-2 and VEGF in endometrial cancer cells.
      【Key words】 Endometrial carcinoma; Metformin; Cyclooxygenase-2 (COX-2); Vascular endothelial growth fac-tor (VEGF); Phosphatase and tensin homolog deleted on chromosome ten (PTEN)