新藤黄酸诱导细胞凋亡抑制A549细胞裸鼠移植瘤增长的研究

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.

Gambogenic acid inhibits proliferation of A549 cells through apoptosis-inducing

To explore gambogenic acid (GNA)-induced apoptosis and underlying mechanism in vivo. A549 nude mice xenografts were used as in vivo model to study anticancer effect of GNA by observing tumor growth curve and weight of the tumor. Ultrastructure of A549 cells treated by GNA was observed by TE. Expression of COX-2 and VEGF were detected by immunohistochemistry. TUNEL assay was applied in examining apoptosis index of tumor cells. The tumor isolated from mice treated by GNA (8,16 mg·kg^-1) took on a slow growth condition compared with control group. The results suggested that weight and volume of the tumor from experimental groups were remarkably decreased compared with control group (P<0.05). Ultrastructure change of the tumor, such as vacuolization, abnormal distribution of the heterochromosome, volume of the tumor cells, even apoptotic bodies, were observed in GNA-treated group. While no apparent morphological change was observed in the normal group. Typical apoptotic characteristics could be distinctly observed in the mouse treated by GNA for 20 days and apoptosis index in GNA-treated group was significantly higher than model group. Expression of COX-2 and VEGF were significantly down-regulated in GNA-treated groups in comparison with control group (P<0.01). These results indicate that GNA could affect the development and progression of A549 cells through inducing apoptosis, mediating the expression of VEGF in vascular cells and COX-2 in tumor cells.