芝麻素对C_(57)BL/6小鼠Lewis肺癌的抑制作用及其机制

Anti-tumor effects and mechanisms of sesamin on Lewis lung cancer in C_(57)BL/6 mice

目的:初步观察芝麻素(Sesamine,Ses)对C57BL/6小鼠Lewis肺癌的抑制作用,并探讨其机制。方法:①体内实验:将传代培养的Lewis肺癌细胞接种于C57BL/6小鼠右腋皮下建立Lewis肺癌模型,成模后的40只小鼠随机分为5组,即模型组[0.5%羧甲基纤维素10 ml/(kg.d)]、Ses低、中、高剂量组[30、60、120 mg/(kg.d)]和阳性对照5-氟尿嘧啶组[5-Fu 128 mg/(kg.d)],连续灌胃给药28 d。计算抑瘤率和脏器系数;免疫组化法表达肿瘤组织中MMP-2和MMP-9;ELISA检测瘤组织TNF-α含量;HE染色观察肿瘤形态学变化;②体外实验:MTT检测细胞抑制率。结果:体内试验显示Ses各剂量组呈剂量依耐性抑制小鼠肿瘤生长,减慢肿瘤增殖速度,减轻瘤重,升高脾脏和胸腺系数,减少MMP-2,MMP-9、TNF-α的表达。光镜下可见瘤细胞排列较稀疏,小片状坏死区,有核固缩和溶解现象。体外实验显示Ses含药血清呈明显的浓度依赖性抑制Lewis肺癌细胞的增殖。结论:Ses对C57BL/6小鼠Lewis肺癌细胞有一定剂量依赖性抑制作用,其机制可能与调节机体的免疫功能、减少细胞外基质降解有关。

Objective：To investigate the inhibitory action and mechanisms of sesamin（Ses） on Lewis lung carcinoma（3LL） in C57BL/6 mice.Methods：①In vivo experiment：We first developed in vivo the experimental models（n=40） by inoculation of 3LL tumors subcultured into the hypoderm of right oxter of C57BL/6 mice and randomly allocated them to 5 groups（n=8 for each）,namely,model group[0.5% carboxymethyl cellulose 10 ml/（kg·d）],Ses administration in dose of low,medium or high[30,60,120 mg/（kg·d）],respectively） and positive controls [5-Fu 128 mg/（kg·d）].The animals were intragastrically administrated for consecutive 28 days.After that,the tumor inhibition rate and organ coefficients were calculated.Content of MMP-2 and MMP-9 in tumor tissues were detected by immunohistochemistry and TNF-α,by ELISA.HE staining was used to observer the morphological changes of the tumor tissues.②In vitro tests：MTT was used to determine the inhibition ratio of cell growth.Results：In vivo findings showed that Ses intervention in a dose of low,medium and high had slightly inhibited tumor growth in C57BL/6 mice and resulted in slow tumor proliferation,reduced tumor weight,increased spleen and thymus coefficient and down-regulated MMP-2,MMP-9 and TNF-α expression by totally dose-dependent correlation.Light microscopy revealed sparse tumor cells,patchy necrosis and nuclear pyknosis and lysis.In vitro tests by determination of the serum containing Ses also demonstrated that it had inhibited the proliferation of 3LL tumors in significant dose-dependent manner.Conclusion：Ses can in vivo and in vitro inhibit Lewis lung cancer cells in C57BL/6 mice in a certain dose-response fashion,and the potential mechanism may be associated with the role of the drug in immune function regulation and reduction of extracellular matrix degradation in animals.