依西美坦联合多烯紫衫醇对人子宫内膜癌裸鼠移植瘤抑制作用的实验研究

吕红伟; 马晓欣; 于宛琳; 贺媛琪

doi:10.3969/j.issn.1000-8179.2011.09.001

摘要: 目的：探讨第三代芳香化酶抑制剂依西美坦和多烯紫衫醇单独及联合用药对人子宫内膜癌裸鼠移植瘤的生长抑制作用及其相应机制。方法：将处于对数生长期的人子宫内膜腺癌Ishikawa细胞接种于裸鼠皮下，建立裸鼠的移植瘤动物模型，将荷瘤裸鼠随机分为4组，每组5只，依西美坦和多烯紫衫醇分别单独及联合处理裸鼠移植瘤模型3周，对照组予以生理盐水3周，计算各组移植瘤体积、抑瘤率及裸鼠体重情况，肿瘤组织标本进行HE染色病理检查，并用TUNEL法（脱氧核苷酸转移酶介导的dUTP缺口末端标记法）检测细胞凋亡情况。结果：依西美坦组、多烯紫衫醇组的抑瘤率分别为25.59%和27.41%，联合用药组的抑瘤率则为47.09%，联合用药组与单独用药组及对照组比较差异均有统计学意义（P<0.05）； TUNEL法检测联合用药组肿瘤细胞凋亡率为（40.14±3.44） %，明显高于单独用药组［依西美坦组（30.92±2.95） %、多烯紫衫醇组（32.65±2.72） %］和对照组（13.52±1.42） %，差异有统计学意义（P<0.05）。结论：依西美坦、多烯紫衫醇均可抑制人子宫内膜癌裸鼠移植瘤的生长，两者联合应用较两药单独应用对人子宫内膜癌裸鼠移植瘤的抑制作用更为显著。

Abstract: Effect of Combined Medication of Exemestane and Docetaxel on the Growth of HumanEndometrial Carcinoma Xenograft in Nude MiceHongwei LV, Xiaoxin MA,Wanlin YU, Yuanqi HECorrespondence to: Xiaoxin MA, E-mail: maxiaoxin666@yahoo.com.cnDepartment of Obstetrics and Gynecology, The Second Affiliated Hospital of China Medical University, Shenyang 110004, ChinaThis study was supported by a special fund of Liaoning Science and Technology Bureau (2007225002-3)Abstract Objective: To investigate the anti-tumor effect of combined medication of Exemestane and Docetaxel on xenograftedtumor growth of human endometrial carcinoma in nude mice and to explore the related molecular mechanisms. Methods: Humanendometrial adenocarcinoma Ishikawa cells were inoculated into athymic nude mice. Twenty nude mice bearing xenografted humanendometrial carcinoma were randomly divided into 4 groups ( n = 5 ). The mice in the experiment group were selected and treated withExemestane and Docetaxel jointly and separately for 3 weeks, and those in the control group were treated with 0.9% sodium chloridefor 3 weeks. After precise calculation of the tumor size, tumor inhibition ratio and bodyweight of the nude mice, TUNEL detection wasused to measure the effect of Exemestane and Docetaxel on cell apoptosis. Results: The inhibition ratios of tumor growth were 25.59%,27.41% and 47.09% respectively in the groups treated with Exemestane, Docetaxel and combined therapy. The inhibition ratio washigher in the combined therapy group than in the Exemestane group and Docetaxel group ( P < 0.05 ). There was statistical significanceamong the 4 groups ( P < 0.05 ). The apoptosis of endometrial carcinoma cells was induced by Exemestane and Docetaxel, and theapoptotic rate was the highest when the cells were treated with combination of the two drugs. The apoptotic rates were ( 30.92 ±2.95)%,( 32.65 ± 2.72 ) % and ( 40.14 ± 3.44 )% in Exemestane group, Docetaxel group and Combined therapy group. The apoptotic rate wassignificantly higher in the combined therapy group than in Exemestane group and Docetaxel group ( P < 0.05 ). Conclusion:Exemestane and Docetaxel can significantly inhibit the growth of human endometrial carcinoma xenografts in nude mice, and thecombination therapy with the two drugs can produce a synergistic action.Keywords Nude mice; Endometrial carcinoma; Exemestane; Docetaxel