冬凌草甲素注射液对人胃腺癌裸鼠移植瘤的抑制作用及其机制

目的 观察冬凌草甲素注射液对BGC823人胃腺癌裸鼠移植瘤的生长抑制作用,并探讨其作用机制.方法 建立裸鼠BGC823人胃腺癌移植瘤模型,并随机分为空白对照组、低剂量组和高剂量组,分别通过尾静脉注射生理盐水、冬凌草甲素注射液37.5 mg·kg-1·d-1和冬凌草甲素注射液75 mg·kg-1·d-1.10 d后,剥出瘤块称移植瘤重量,光镜及电镜下观察移植瘤组织形态学及瘤细胞的超微结构变化,免疫组化SABC法检测移植瘤bcl-2、Bax、Fas和FasL蛋白的表达差异.结果 冬凌草甲素注射液可抑制裸鼠BGC823人胃腺癌移植瘤的生长,低剂量组与高剂量组的抑瘤率分别为48.5%和70.7%.病理形态学显示,冬凌草甲素注射液作用后移植瘤出现细胞凋亡及组织坏死.免疫组化检测显示,冬凌草甲素注射液作用后瘤组织中bcl-2蛋白表达减少,Bax、Fas和FasL蛋白表达增加.结论 冬凌草甲素注射液可显著抑制BGC823人胃腺癌裸鼠移植瘤的生长,其作用机制与诱导肿瘤细胞凋亡有关.

Inhibitory effect of Oridonin injection on heterotransplanted gastric adenocarcinoma in nude mice and its mechanism

OBJECTIVE: To investigate the inhibitory effect of Oridonin injection on heterotransplanted tumors of human gastric adenocarcinoma cell line BGC823 cells in nude mice and explore its mechanism. METHODS: Heterotransplanted models of human gastric adenocarcinoma cell line BGC823 cells in nude mice were established. They were divided at random into three groups as control group, low-dose group and high-dose group. The Oridonin solution at concentration of 37.5 mg x kg(-1 x d(-1) and 75 mg x kg(-1) x d(-1) were injected to the mice in low-dose group and high-dose group, respectively, and 0.9% sodium chloride was injected to the mice of control group per day for 10 days sequentially. The mice of the three groups were sacrificed at 11th day after the first injection of Oridonin. The tumor weight of the sacrificed mice was measured. Morphological and ultrastructural examinations of the tumors were carried out by light and electron microscopy. The expression of bcl-2, Bax, Fas and FasL was detected by immunohistochemistry. RESULTS: Oridonin injection showed a suppressive effect on the growth of heterotransplanted tumors in the nude mice. The tumor growth inhibition rates were 48.5% and 70.7% in the low-dose and high-dose groups, respectively. The morphological study demonstrated that tumor cells displayed a typical appearance of apoptosis. The expression of bcl-2 was down-regulated, while Bax, Fas and FasL were up-regulated. CONCLUSION: Oridonin can markedly inhibit the growth of heterotransplanted human gastric adenocarcinoma in nude mice. It was due, at least in part, to the induction of apoptosis in cancer cells.