RY10-4对乳腺癌MCF-7裸鼠移植瘤的抑制作用及其机制

发布时间：2018-04-15 03:37

本文选题：RY- + 移植瘤　；参考：《中国医院药学杂志》2015年15期

【摘要】：目的:探讨2-(1-羟基-4-酮-2,5-环己二烯)-吡喃-4-酮(RY10-4)对乳腺癌裸鼠移植瘤抑制作用及其可能的作用机制。方法:建立乳腺癌(MCF-7)裸鼠移植瘤模型,将造模裸鼠随机分为模型组、RY10-4低剂量组(7.5 mg·kg-1)、RY10-4高剂量组(15 mg·kg-1)和紫杉醇组(15 mg·kg-1);各组均采取隔天腹腔注射给药,检测各组荷瘤裸鼠移植瘤体积和体质量变化。给药16 d后,处死所有裸鼠,称取各组移植瘤质量,TUNEL法检测凋亡指数,并通过Western blot测定移植瘤中Bcl-2、Bax和MAPK通路蛋白的表达。结果:与模型组比较,RY10-4低、高治疗组和紫杉醇组瘤体积明显减小,瘤质量明显减轻,抑瘤率分别为29.8%,47.2%,53.8%。TUNEL法结果显示,各治疗组能明显引起移植瘤细胞凋亡(P0.01)。Western blot结果显示,随着RY10-4治疗量的增加抗凋亡蛋白Bcl-2表达减弱,促凋亡蛋白Bax的表达增强,Bcl-2/Bax值显著下降,与模型组相比差异均有统计学意义(P0.05);另外,RY10-4治疗组移植瘤细胞中的p-p38和p-ERK表达量明显增加。结论:RY10-4能够抑制乳腺癌移植瘤的生长和诱导乳腺癌细胞的凋亡,其诱导凋亡作用可能与下调Bcl-2蛋白和上调Bax蛋白,降低Bcl-2/Bax值,并激活p38和ERK信号通路有关。
[Abstract]:Aim: to investigate the inhibitory effect of 2-OH-1-hydroxy-4-ketone-5-cyclohexadiene-pyrrolidene (RY10-4) on breast cancer xenografts in nude mice and its possible mechanism.Methods: the transplanted tumor model of breast cancer MCF-7) was established in nude mice. The nude mice were randomly divided into model group (RY10-4 low dose group) and high dose group (RY10-4 high dose group (15 mg kg-1) and paclitaxel group (15 mg kg -1).The volume and body mass of transplanted tumor in nude mice were measured.After 16 days of administration, all nude mice were killed and the apoptotic index was detected by Tunel method. The expression of Bcl-2 Bax and MAPK pathway proteins were detected by Western blot.Results: compared with the model group, RY10-4 was lower. The tumor volume and tumor quality of the high treatment group and paclitaxel group were significantly reduced, and the tumor inhibition rate was 29.87.2and 53.8. Tunel respectively. The results of Tunel method showed that the apoptosis of transplanted tumor cells was obviously induced by P0.01.Western blot in each treatment group.With the increase of RY10-4 treatment dose, the expression of anti-apoptotic protein Bcl-2 decreased, while the expression of pro-apoptotic protein Bax increased and Bcl-2 / Bax decreased significantly.In addition, the expression of p-p38 and p-ERK in transplanted tumor cells in RY10-4 group was significantly increased compared with the model group.Conclusion: RY10-4 can inhibit the growth of breast cancer xenografts and induce apoptosis of breast cancer cells, which may be related to down-regulation of Bcl-2 protein and up-regulation of Bax protein, decrease of Bcl-2/Bax value, and activation of p38 and ERK signaling pathway.
【作者单位】：华中科技大学同济药学院;
【基金】：武汉市科学技术发展基金(编号:201260523182)
【分类号】：R965

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