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目的:通过体内移植瘤模型探讨新藤黄酸干预人非小细胞肺癌的发生发展的可能机制。方法:采用肺腺癌A549裸鼠移植瘤实验,评价新藤黄酸对人肺腺癌裸鼠移植瘤生长的抑制作用;透射电镜观察细胞超微结构的变化;TUNEL法检测凋亡指数;免疫组织化学方法检测瘤体组织COX-2和VEGF蛋白的表达。结果:新藤黄酸8,16 mg.kg-1给药后裸鼠的移植瘤较模型组生长缓慢,瘤重及瘤体积明显低于模型组(P<0.01);透射电镜观察发现新藤黄酸各组肿瘤细胞出现典型的凋亡特征;模型组中癌细胞质无明显空泡化,核膜内侧异染色质区域表现正常,其他染色质正常分散分布;TUNEL结果表明,给药组瘤体组织的凋亡指数明显高于模型组;免疫组织化学分析结果显示新藤黄酸作用后能够降低肿瘤组织的COX-2和VEGF的表达(P<0.01)。结论:新藤黄酸可能通过诱导肺腺癌A549细胞凋亡而干预人非小细胞肺癌的发生发展,并调控肿瘤组织VEGF和COX-2蛋白的表达。
OBJECTIVE: To explore the possible mechanism of new gambogic acid intervention in the development of human non-small cell lung cancer (NSCLC) by in vivo xenograft model. Methods: The A549 lung adenocarcinoma xenografts in nude mice were used to evaluate the inhibitory effect of new gambogic acid on the growth of human lung adenocarcinoma xenografts in nude mice. The ultrastructural changes of the cells were observed by transmission electron microscopy. The apoptotic indexes were detected by TUNEL assay. The chemical method was used to detect the expression of COX-2 and VEGF protein in tumor tissues. Results: The transplanted tumor of nude mice grew slowly and the tumor weight and tumor volume were significantly lower than those of model group (P <0.01) after 8,16 mg.kg-1 administration of new Gambogic acid. Transmission electron microscope The typical apoptotic characteristics of tumor cells in each group showed no obvious vacuolization of the cytoplasm, normal distribution of heterochromatin in the inner nuclear membrane, and normal distribution of other chromatin in the model group. TUNEL results showed that the tumor tissue The apoptotic index was significantly higher than that of model group. Immunohistochemical analysis showed that the effect of new Gambogic acid could reduce the expression of COX-2 and VEGF (P <0.01). Conclusion: Gambogic acid may interfere with the development of human non-small cell lung cancer by regulating the apoptosis of lung adenocarcinoma A549 cells and regulate the expression of VEGF and COX-2 in tumor tissues.