三氧化二砷联合热疗抑制大鼠肝癌的体内实验研究

目的:研究热疗联合三氧化二砷(As2O3)对大鼠肝癌多药耐药性的影响,探讨其作为肝癌辅助治疗的可行性。方法:采用含有walker-256肿瘤细胞的大鼠腹水稀释后接种于大鼠腹股沟皮下,7天后取下瘤块并切成(1.0-2.0)mm3大小的小块,然后将小瘤块接种于50只大鼠的左肝叶上,10天后将大鼠分成4组,分别为对照组,热疗组,As2O3组及(热疗+As2O3)组,同时给予治疗,治疗结束后第2天处死大鼠。测量瘤重分析As2O3联合热疗的体内抑瘤作用;用H-E染色法观察肿瘤细胞病理象变化;免疫组化S-P法检测肿瘤组织内Pgp(P-glycoprotein,P-糖蛋白)的表达情况。结果:热疗组,As2O3组及(热疗+As2O3)组的平均瘤重均低于对照组(P<0.05);同时(热疗+As2O3)组与As2O3组及热疗组相比较,前者抑瘤率高于后两者(P<0.05)。在实验过程中,对照组荷瘤鼠活动减少,毛发稀疏,进食水少,而热疗组大鼠活动稍差,其余两组基本正常,饮食状况无明显改变,体重未见明显减轻。各组细胞均有坏死,大部分为凝固性坏死。对照组肿瘤细胞生长比较旺盛,坏死面积较小。其他三组坏死都比较彻底,并且呈现大片状坏死,尤以(热疗+As2O3)组明显,镜下呈一片荒凉景象,肿瘤细胞溶解,破碎,多见细胞核碎裂及核固缩表象。免疫组化法观察到多药耐药细胞呈片状分布,Pgp主要分布于耐药细胞的胞膜面,少数分布于胞浆当中;Pgp显色指数在对照组与各处理组之间差异显著(P<0.05),且(热疗+As2O3)组较其他处理组差异显著(P<0.05)。结论:As2O3和热疗在体内对大鼠肝癌均有明显的抑制作用,两者联合应用有协同作用,其作用机制可能与抑制多药耐药基因(MDR1)的表达有关。

Inhibitory effect of Arsenic trioxide (As2O3) combined with thermotherapy on hepatocarcinoma of rats in vivo

Objective:To study the effects of thermotherapy and Arsenic trioxide(As2O3) on multidrug resistance gene 1 of hepatocarcinoma in rats,and to explore the feasibility of using it as a new therapeutic method for liver cancer.Methods:Rats received ascites diluted containing walker-256 cells at inguen subcutaneously.Seven days later tumor issues were taken from the rats and cut to 1-2mm3 pieces which were translanted at hepatic lobes of another 50 rats.The rats were randomly assigned into 4 groups ten days latet...