目的 探究右美托咪定对子宫内膜癌细胞增殖、凋亡及Wnt/β-连环蛋白（β-catenin）通路的影响。方法 将Ishikawa、RL95-2细胞分为对照组，右美托咪定1、10、100 nmol/L组，右美托咪定（100 nmol/L）＋LiCl组。CCK-8法和EdU检测细胞增殖，流式细胞术检测细胞凋亡，Western blotting检测增殖细胞核抗原（PCNA）、B淋巴细胞瘤-2蛋白（Bcl-2）、Bcl-2相关X蛋白（Bax）、β-连环蛋白（β-catenin）、c-Myc基因（c-Myc）、细胞周期蛋白D1（Cyclin D1）表达水平。构建子宫内膜癌裸鼠模型，分为对照组、右美托咪定组、右美托咪定＋LiCl组，测量肿瘤质量与体积，苏木精–伊红（HE）染色观察移植瘤组织形态，免疫组化法检测移植瘤组织Ki-67、β-catenin蛋白表达。结果 与对照组相比，不同浓度右美托咪定处理后Ishikawa、RL95-2细胞吸光度（A）值、EdU阳性细胞率、迁移细胞数、侵袭细胞数、PCNA、Bcl-2、β-catenin、c-Myc、Cyclin D1蛋白表达显著降低，凋亡率、Bax表达上升（P＜0.05）；与右美托咪定100 nmol/L组相比，右美托咪定＋LiCl组A值、EdU阳性细胞率、迁移细胞数、侵袭细胞数、PCNA、Bcl-2、β-catenin、c-Myc、Cyclin D1蛋白表达显著升高，凋亡率、Bax表达下降（P＜0.05）。右美托咪定能抑制移植瘤质量和体积，促进肿瘤凋亡，降低β-catenin、Ki-67蛋白表达（P＜0.05）；LiCl能逆转右美托咪定对移植瘤的抑制作用（P＜0.05）。结论 右美托咪定能抑制子宫内膜癌细胞增殖，促进凋亡，其作用机制可能与抑制Wnt/β-catenin信号通路有关。

Objective To investigate the impacts of dexmedetomidine on the proliferation, apoptosis, and Wnt/β-catenin pathway of endometrial cancer cells. Methods Ishikawa and RL95-2 cells were divided into control group, dexmedetomidine 1, 10, 100 nmol/L, and dexmedetomidine (100 nmol/L) + LiCl group. CCK-8 method and EdU were applied to detect cell proliferation, flow cytometry was applied to detect cell apoptosis, Western blotting was applied to detect the expression levels of PCNA, Bcl-2, Bax, β-catenin, c-Myc, and cyclin D1. An endometrial cancer nude mice model was constructed and divided into control group, dexmedetomidine group, and DEX + LiCl group, the mass and volume of the tumor are measured, HE staining was applied to observe the morphology of transplanted tumor tissue, immunohistochemical methods were applied to detect the expression of Ki-67 and β-catenin proteins in transplanted tumor tissue. Results Compared with control group, the A value, EdU positive cell rate, migration cell number, invasion cell number, PCNA, Bcl-2, β-catenin, c-Myc, and Cyclin D1 protein expression of Ishikawa and RL95-2 cells were obviously reduced after treatment with different concentrations of dexmedetomidine, the apoptosis rate and Bax expression increased (P < 0.05). Compared with dexmedetomidine 100 nmol/L group, the A value, EdU positive cell rate, migration cell number, invasion cell number, PCNA, Bcl-2, β-catenin, c-Myc, and Cyclin D1 protein expression in dexmedetomidine + LiCl group obviously increased, the apoptosis rate and Bax expression decreased (P < 0.05). Dexmedetomidine was able to inhibit the mass and volume of transplanted tumors, promote tumor apoptosis, and reduce the expression of β-catenin and Ki-67 proteins (P < 0.05), LiCl reversed the inhibitory effect of dexmedetomidine on transplanted tumors (P < 0.05). Conclusion Dexmedetomidine can inhibit proliferation and promote apoptosis of endometrial cancer cells, and its mechanism of action may be related to the inhibition of the Wnt/β-catenin signaling pathway.

R965

石家庄市科学技术研究与发展计划项目（211200883）