双氢青蒿素对Lewis肺癌小鼠的抑瘤作用及其机制探讨

Inhibitory effect of Dihydroarteannuin in Lewis lung cancer C57BL/6J mice

目的探讨双氢青蒿素对Lewis肺癌小鼠的抑瘤效应及其作用机制。方法C57BL/6J小鼠皮下接种3LL细胞(2×106)50只,随机分为5组,分别为生理盐水组、阳性对照顺铂组、双氢青蒿素高、中、低剂量组,检测各组小鼠的体重变化和抑瘤率,应用流式细胞术进行TUNEL分析和凋亡相关基因及其表达改变的检测。结果双氢青蒿素中、高剂量组体重较生理盐水组增加明显,其抑瘤率分别为53.5%及59.2%;流式细胞术TUNEL检测结果显示,其作用细胞凋亡和坏死同时存在。FCM法分析其对肺癌组织凋亡相关基因检测表明中、高剂量组Fas、p53等凋亡基因上调,Bcl-2抑制凋亡基因下调。结论双氢青蒿素对Lewis肺癌小鼠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。

Objective To study the anti-tumor effect and the mechanism of Dihydroarteannuin （DHA） in lung cancer hearing C57BL/6J mice. Methods C57BL/6J mice subcutaneously planted with 3LL lung cancer cell （2 ×10^6） were randomly divided into 5 groups：blank control group,same volume of normal saline group; positive control DDP group; DHA low, middle and high dose groups. The body weight changes and inhibitory rate of mice in each group were observed. In addition, the TUNEL of lung cancer cell and the expression of apoptosis associated gene were analysed by flow cytometry. Results Body weight was decreased in middle and high dose groups compared with normal saline group and the resistant rate was 53.5% and 59.2% ,respectively. By flow cytometry,the result of TUNEL indicated that there were apoptosis and necrosis. Both in middle dose group and high dose group,the expression of apoptosis associated gene Fas and p53 was up regulated,the Bcl-2 down regulated. Conclusions Dihydroarteannuin is provided with anti-tumor effect to lung cancer bearing C57BL/6J mice at certain range of dosage. It can induce apoptosis of lung cancer cell. Its mechanism might relate to modulation of the apoptosis associated gene expression.