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 iBaues were taken from the rats and cut to 1 -2mm3 pieces which were translanted at hepatic lobes of another 50rats.The rats were randomly assigned into 4 groups ten days latetr included conrrol group, thermotherapy, As2 O1 therapy, and combination therapy group initiated ten days later and the rats sacrificed on the second days after the treatments were finished.The weight of tumor was measured to analyze inhibition rate ; Pathological changes of tumor tissue were observed by H - E stainning;MDR1 protein expression were measured by S - P immunohistochemical staining.Results: Tumor growth were inhibited in combination therapy group , thermotherapy group and As2 O3 group ( P＜0.05) .But the combination therapy had more significant antitumor activity ( P ＜0.05).The patholopcal examination showed there was cellular necrosis in all sections, and was almost coagulation riecrosis.In control group tumor ceIIs multiplied quickly, and where were slight necrosis.Foliated necrosis happened in other groups, especially in combination group where were desolate scene including cytolysis , cytoclasis , nuclear fragmentation and pycnosis.Companng with control group , the expression of MDR1 in other groups decreased ( P ＜ 0.05 ) , funhermore the expression of MDR1 of the combination groups was lower than the other two groups ( P ＜ 0.05) .Conclusion : As2 O3 or thermotherapy inhibited tumor growth, and As2O3 had apparente synergistic effects with thermotherapy in inhibiting hepatocarcinoma growth.One mechanism may be the decreased expression of MDR1.%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.
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