美洲大蠊提取物对小鼠3LL肺癌的抑制作用及其机制探讨

Inhibitory effect of Periplaneta Americana extract on 3LL lung cancer in mice

背景与目的美洲大蠊系列昆虫药品康复新在体外能诱导多种肿瘤细胞系发生细胞凋亡。本研究旨在探讨美洲大蠊提取物对C57BL/6J小鼠3LL肺癌的抑制效应及其作用机制。方法荷3LL肺癌的C57BL/6J小鼠随机分为生理盐水组、美洲大蠊提取物高、低剂量组,通过检测各组小鼠的体重变化和抑瘤率,应用流式细胞术进行DNA倍体分析、TUNEL分析和凋亡相关基因表达改变的检测。结果与生理盐水组比较,美洲大蠊提取物高、低剂量组的抑瘤率分别为41.24%及81.08%。流式细胞术检测美洲大蠊提取物能诱导肿瘤细胞凋亡,随着药物剂量的增高,其凋亡率也升高,S期及G2/M期细胞数大量减少,细胞被阻滞在G0/G1期;流式细胞术TUNEL检测结果显示,细胞凋亡和坏死同时存在。流式细胞法分析3LL肺癌细胞凋亡相关基因显示,无论是低剂量组还是高剂量组,美洲大蠊提取物均能上调Fas、FasR、p53等凋亡基因表达,下调Bcl-2抑制凋亡基因表达。结论美洲大蠊提取物对3LL肺癌生长具有一定的抑制作用,能促进肿瘤细胞凋亡,其机制可能与调控细胞凋亡相关基因的表达有关。

Background and objective It has been known that Kangfuxin, a drug derived from Periplaneta Americana, can induce cell apoptosis of many cancer cell lines in vitro. The aim of this study is to investigate the inhibitory effect and mechanism of Periplaneta Americana extract （PAE） on 3LL lung cancer in mice. Methods The C57BL/6J mice transplanted with 3LL lung cancer were divided into normal saline （NS）, PAE high dose （PAE-H） and PAE low dose （PAE-L） groups. The body weight changes and inhibitory rate of tumor growth in each group were observed. In addition, the cell cycle, apoptosis index （AI） and the expression of apoptosis associated genes were analysed by flow cytometry （FCM）. Results The body weights were decreased in PAE-L and PAE-H treated group compared with NS group and the inhibitive rate of tumor growth was 41.24% and 81.08% respectively. FCM assay indicated that PAE could induce apoptosis of lung cancer cell, and the apoptosis rate was concentration-dependent. At the same time, the number of S and G2/M phase cells was decreased, most of the cells were arrested in G1/G1 phase. The result of TUNEL showed that there were apoptosis and necrosis associated with upregulated expression of Fas, FasR and p53 genes, and downregulated expression of Bcl-2. Conclusion PAE may inhibit the growth of 3LL lung cancer in mice and induce apoptosis of 3LL lung cancer cells. It might be related to its effects on the regulation of apoptotic gene expression.