作者：赵轶峰1，李明霞2，章帅1，李云1，张育1，毕仁杰1，李曙光1

单位：1.河北北方学院附属第一医院 胃肠肿瘤外科， 河北 张家口 075000;  2.河北北方学院附属第一医院 内分泌科， 河北 张家口 075000

Authors: Zhao Yifeng1, Li Mingxia2, Zhang Shuai1, Li Yun1, Zhang Yu1, Bi Renjie1, Li Shuguang1

Unit: 1.Department of Gastrointestinal Tumor Surgery, the First Hospital Affiliated to Hebei North University, Zhangjiakou 075000, Hebei, China;  2.Department of Endocrinology, the First Hospital Affiliated to Hebei North University, Zhangjiakou 075000, Hebei, China

摘要：

目的 探究雌二醇是否是影响胃癌发病性别差异的关键因素，并从雌激素受体（ER）方面探讨可能的机制。方法 选取2012年6月至2020年3月河北北方学院第一附属医院收治的胃癌患者372例，对患者的性别、年龄、病理学分型等临床资料进行统计分析。通过建立异种移植瘤小鼠模型来观察性别对胃癌细胞EC109异种移植瘤的影响。体外培养胃癌EC109细胞激光共聚焦显微镜检测ERα和ERβ的表达。通过细胞活力和迁移能力分析在细胞水平上雌激素抗肿瘤效应的可能机制。结果 胃癌的入院患者中男性高于女性（男91.13%，女8.87%,P<0.05）。胃癌细胞异种移植模型结果表明，雌性小鼠的异种移植物重量体重之比低于雄性小鼠，与雄性组比较，雌性组的抑瘤率高达73.65%。细胞免疫荧光检测显示，ERα在胃癌的细胞核中表达，ERβ则检测不到。细胞迁移能力结果显示，雌二醇降低胃癌细胞迁移能力，ER拮抗剂抵消了雌二醇对胃癌细胞迁移能力的影响，ERS抑制剂可以对抗雌二醇对胃癌细胞迁移能力的抑制效应，ER激动剂可增强雌二醇对胃癌细胞迁移能力的抑制效应。细胞生长活力结果与细胞迁移能力结果具有相同的趋势。结论 性别差异参与胃癌的发生发展，雌二醇通过ERα抑制胃癌细胞的活力和迁移。 

关键词：胃癌； 性别； 雌激素； 雌激素受体

Abstract：

Objective To explore whether estradiol is a key factor affecting gender differences in gastric cancer，and to explore the possible mechanism from estrogen receptors. Method A total of 372 patients with gastric cancer admitted to the First Affiliated Hospital of Hebei North University from June 2012 to March 2020 were included in this study. The clinical data of the patients，including gender，age，and pathological type，were analyzed to explore the effects of gender. The effect of gender on EC109 xenograft tumours was observed by establishing a xenograft tumour mouse model. The expression of estrogen receptor （ER） α and ERβ in gastric cancer EC109 cells cultured in vitro was detected by laser confocal microscopy ， and the cell viability and migration capacity were analyzed to observed the effect of estrogen on gastric cancer cells in vitro. Result The male patients were significantly higher than the female patients （91.13%：8.87%，P<0.05）. The results of the gastric cancer cell xenograft model showed that the xenograft weight and the ratio of xenograft weight to body weight of female mice were lower than those of male mice ，and the tumor inhibition rate of female mice was as high as 73.65% compared with the male group. Immunofluorescence assay showed that ERα was expressed in the nucleus of gastric cancer，but ERβ was not detected. The cell migration capacity results showed that estradiol decreased the migration capacity of gastric cancer cells ，ER antagonists counteracted the effect of estradiol on the migration capacity of gastric cancer cells ，ERS inhibitors counteracted the inhibitory effect of estradiol on the migration capacity of gastric cancer cells ，and ER agonists enhanced the inhibitory effect of estradiol on the migration capacity of gastric cancer cells. The cell growth viability results showed the same trend as the cell migration ability results. Conclusion Gender are involved in the development of gastric cancer and estradiol inhibits the viability and migration of gastric cancer cells via ERα.

Key Words:  Gastric cancer; Sex; Estrogen; Estrogen receptor