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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(P<0.01)。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(P<0.05);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。
Objective: To investigate the inhibitory effect of 2- (1-hydroxy-4-keto-2,5-cyclohexadiene) -pyran-4-one (RY10-4) on breast cancer xenografts in nude mice and its possible mechanism . Methods: The nude mice model of breast cancer (MCF-7) was established. The nude mice were randomly divided into model group, RY10-4 low dose group (7.5 mg · kg -1), RY10-4 high dose group mg · kg-1) and paclitaxel group (15 mg · kg-1). The mice in each group were given intraperitoneal injection every other day to detect the tumor volume and body weight of nude mice in each group. Sixteen days after the administration, all the nude mice were sacrificed, and the tumor weight of each group was weighed. The apoptosis index was measured by TUNEL method. The expression of Bcl-2, Bax and MAPK pathway proteins in the xenografts was detected by Western blot. Results: Compared with the model group, the tumor volume of RY10-4 low, high treatment group and paclitaxel group was significantly reduced, and the tumor mass was significantly reduced. The tumor inhibition rates were 29.8%, 47.2% and 53.8% respectively. The results of TUNEL showed that each treatment group could obviously induce the apoptosis of tumor cells (P <0.01). Western blot results showed that with the increase of RY10-4 treatment, the expression of anti-apoptotic protein Bcl-2 was weakened, the expression of pro-apoptotic protein Bax was increased, and the Bcl-2 / Bax value was significantly decreased, compared with the model group (P <0.05). In addition, the expression of p-p38 and p-ERK in the tumor cells of RY10-4 treatment group was significantly increased. CONCLUSION: RY10-4 can inhibit the growth of breast cancer xenografts and induce the apoptosis of breast cancer cells. The apoptosis induced by RY10-4 may be related to the down-regulation of Bcl-2 protein and up-regulation of Bax protein, decrease of Bcl-2 / Bax and activation of p38 And ERK signaling pathway.