来曲唑联合姜黄素对人子宫内膜癌细胞裸鼠移植瘤生长的影响

Inhibiting effect of letrozole combined with curcumin on xenografted endometrial carcinoma growth in nude mice

背景与目的:芳香化酶抑制剂来曲唑能够抑制子宫内膜癌细胞的生长,但抑制率不理想。近年来的研究表明,姜黄素有一定的抗肿瘤作用,且还可以增加肿瘤细胞对化疗药物的敏感性。本研究旨在探讨来曲唑与姜黄素联合对人子宫内膜癌裸鼠移植瘤细胞增殖的抑制作用。方法:将人子宫内膜癌细胞株RL-952接种于裸鼠皮下,建立裸鼠的移植瘤动物模型。将实验裸鼠随机分成5组,分别给予包括来曲唑、姜黄素在内的药物干预。8周后记录裸鼠体重,计算移植瘤体积、抑瘤率。流式细胞术检测细胞周期及凋亡情况,RT-PCR和Western blot法检测bcl-2mRNA和蛋白的表达。结果:来曲唑低剂量组、来曲唑高剂量组、姜黄素组以及联合用药组的抑瘤率分别为15.95%、22.49%、21.57%和35.89%,对照组肿瘤体积增长明显,来曲唑组(包括高浓度和低浓度)裸鼠肿瘤体积增长相对缓慢,与对照组相比差异有明显统计学意义(P<0.01);来曲唑与姜黄素联合能更有效地抑制裸鼠肿瘤体积增长。对照组、来曲唑低浓度组、来曲唑高浓度组、姜黄素组及联合用药组细胞凋亡率分别为16.97%、32.90%、35.80%、34.16%、47.24%。姜黄素组肿瘤细胞内bcl-2的表达明显降低,尤其是联合用药组明显低于对照组。结论:来曲唑和姜黄素能够抑制RL-952细胞裸鼠移植瘤的生长,其作用机制可能是促进肿瘤细胞的凋亡,联合用药能明显提高其对肿瘤的抑制作用。

Background and Objective：Letrozole is an aromatase inhibitor that is used in the treatment of estrogen-sensitive tumors such as endometrial carcinoma,however,its therapeutic effect is still to be further improved.It is reported that curcumin has antitumor capability and can enhance the sensitivity of tumor cells to anticancer agents.This study was to investigate the inhibitory effect of letrozole combination with curcumin on the implanted endometrial tumor growth.Methods：Nude mice were implanted with endometrial carcinoma RL-952 cells.All tumor-bearing mice were randomly divided into 5 groups：control （without treatment）,Let（1） （letrozole,1 μg /d）,Let（10） （letrozole,10 μg /d）,Cur [curcumin,300 mg /（kg·d）],and Let ＋ Cur group [10 μg /d letrozole ＋ 50 mg /（kg·d） curcumin].The tumor growth was monitored.Tumor cell apoptosis was detected in both control and treated groups.The expressions of bcl-2 mRNA and bcl-2 protein were detected using RT-PCR and Western blot,respectively.Results：Fifty mice were successfully implanted with the endometrial tumor.Treatment with letrozole markedly inhibited tumor growth the inhibitory effect was further enhanced by the combination of letrozole and curcumin.The inhibitory rates in Let （1）,Let （10）,the Cur,and the Let＋Cur groups were 15.95%,22.49%,21.57%,and 35.89%,respectively.Treatment with curcumin inhibited the expression of bcl-2 in tumor cells at the mRNA and protein levels.The apoptosis rates in the control group and the four experimental groups mentioned above were 16.97%,32.90%,35.80%,34.16%,and 47.24%,respectively.Tumor cell apoptosis was observed in mice treated with either letrozole or curcumin however,combination of letrozole and curcumin further enhanced the inhibitory rate in tumor growth.Conclusions：Treatment with either letrozole or curcumin could inhibit the xenografted endometrial tumor growth by inducing apoptosis in tumor cells.Combination of letrozole and curcumin further enhanced the inhibitory effect on tumor growth.