多伞阿魏对人胃癌MGC-803裸鼠移植瘤生长及凋亡的影响

Effect of Ferula ferulaeoides on growth and apoptosis of human gastric cancer MGC-803 transplantation tumor in nude mice

该文系统研究了多伞阿魏活性部位对人胃癌MGC-803细胞裸鼠移植瘤生长及凋亡的影响。采用细胞悬液种植法建立人胃癌MGC-803裸鼠皮下异位移植性肿瘤模型,通过抑瘤率、脏器指数等评价多伞阿魏活性部位对移植瘤生长的影响。采用HE染色法、TUNEL染色法、RT-PCR法、Western-blot法、ELISA法分别进行病理学检查,凋亡情况观察,以及凋亡相关基因、蛋白、细胞因子表达水平检测。结果表明,与模型组比较,多伞阿魏活性部位低、中、高剂量组对裸鼠移植瘤均有不同程度的抑制作用,随着药物浓度的增加,凋亡比率增高。与模型组比较,多伞阿魏可下调裸鼠血液中survivin mRNA表达水平,不同程度升高裸鼠肿瘤组织中Bax,Bcl-2,caspase-3和caspase-9蛋白表达水平;多伞阿魏活性部位高剂量组可下调裸鼠血浆中IL-10和TGF-β1含量。结果表明,多伞阿魏能显著抑制人胃癌MGC-803皮下异位移植瘤的生长,其作用机制可能与下调survivin mRNA表达水平,上调凋亡相关蛋白Bax,caspase-3和caspase-9等表达水平有关。

In this paper,the effects of active fractions of Ferula ferulaeoides on the growth and apoptosis of human gastric cancer cell MGC-803 transplantation tumor were systematically studied.The subcutaneous ectopic transplantation tumor model was established in human gastric cancer MGC-803 nude mice by cell suspension implantation method.The anti-tumor rate and organ index were used to evaluate the anti-tumor effect of the active fractions of F.ferulaeoides on the tumor-bearing nude mice.HE staining,TUNEL staining,RT-PCR,Western-blot and ELISA were used for pathological examination,apoptosis observation,and detection of apoptosis-related genes,proteins and cytokines expression.The results showed that as compared with the model group,the low,medium and high doses of the active fraction of F.ferulaeoides had inhibitory effects on xenografts in nude mice,respectively,in a dose-dependent manner;the apoptotic ratio was increased with the increase of drug concentration.As compared with the model group,F.ferulaeoides could down-regulate the expression of survivin mRNA in nude mice,and the protein expression levels of Bax,Bcl-2,caspase-3 and caspase-9 in tumor tissues of nude mice could be increased to different degrees in F.ferulaeoides groups.The contents of IL-10 and TGF-β1 in plasma of nude mice were decreased in high dose group of F.ferulaeoides active fractions.The results indicated that F.ferulaeoides can significantly inhibit the growth of human gastric cancer MGC-803 subcutaneously transplanted tumor,and its mechanism may be related with down-regulating the expression of survivin mRNA,and up-regulating the expression of apoptosis-related proteins Bax,caspase-3 and caspase-9.