二甲双胍联合顺铂注射液治疗子宫内膜癌抗癌相关机制研究

Study on anticancer mechanism of metformin combined with cisplatin injection in the treatment of endometrial cancer

目的:观察二甲双胍联合顺铂注射液治疗子宫内膜癌的临床效果,探讨二甲双胍可能的抗癌机制。方法:选取广西百色市人民医院妇科2014年6月至2019年5月收治的子宫内膜癌患者240例,随机分为对照组和观察组,每组120例。对照组给予紫杉醇+顺铂(TC方案)治疗,观察组给予TC方案+口服二甲双胍治疗。采用实体瘤疗效评价标准(RECIST)1.1版本评价两组患者近期疗效。分别于化疗前和化疗结束时检测两组患者血清糖类抗原125(CA125)、人附睾分泌蛋白4(HE4)、胰岛素样生长因子1(IGF-1)、哺乳动物雷帕霉素靶蛋白(mTOR)、谷胱甘肽过氧化物酶-1(GPX1)、缺氧诱导因子-1α(HIF-1α)水平。结果:观察组治疗后2个月客观缓解率(ORR)明显高于对照组(58.33%vs. 36.67%,P<0.05)。观察组化疗后血清CA125、HE4、IGF-1、mTOR、HIF-1α水平显著低于对照组,GPX1水平明显高于对照组(P<0.05)。结论:二甲双胍能够提高顺铂方案治疗子宫内膜癌的近期疗效,这可能与二甲双胍下调mTOR和IGF-1表达,通过上调GPX1调节HIF-1α进而增强子宫内膜癌细胞对顺铂的敏感性有关。

Objective: To observe the clinical effect of metformin combined with cisplatin injection in the treatment of endometrial cancer, and to explore the possible anticancer mechanism of metformin. Methods: 240 patients with endometrial cancer admitted to the Gynecology Department of People’s Hospital of Baise from June2014 to May 2019 were selected and randomly divided into a control group and an observation group, with 120 cases in each group. The control group was given paclitaxel + cisplatin(TC therapy), and the observation group was given TC therapy + oral metformin. The 1.1 version of response evaluation criteria in solid tumors(RECIST)was used to evaluate the short-term efficacy in the two groups. The levels of serum carbohydrate antigen 125(CA125), human epididymis protein 4(HE4), insulin-like growth factor 1(IGF-1), mammalian target of rapamycin(mTOR), glutathione peroxidase-1(GPX1), and hypoxia-inducible factor-1α(HIF-1α) were detected before and after chemotherapy. Results: The ORR in the observation group was significantly higher than that in the control group after 2 months of treatment(58.33% vs. 36.67%, P<0.05). After chemotherapy, the serum CA125,HE4, IGF-1, mTOR, and HIF-1α levels in the observation group were significantly lower than those in the control group, and the GPX1 level in the observation group was significantly higher than that in the control group(P<0.05). Conclusion: Metformin can improve the short-term efficacy of cisplatin therapy in the treatment of endometrial cancer, which may be related to down-regulation of mTOR and IGF-1 expression and up-regulation of upregulation of GPX1 to regulate HIF-1α, thereby enhancing the sensitivity of endometrial cancer cells to cisplatin.