Saika T
Department of Urology, Okayama University Medical School.
Nihon Hinyokika Gakkai Zasshi. 1992 May;83(5):643-9. doi: 10.5980/jpnjurol1989.83.643.
Metallothionein (MT) in tumor cell has been indicated as one of the factors involved in the mechanism of resistance to anticancer drugs. The relationship between expression of MT and chemotherapy with anticancer drugs was studied with bladder cancer culture cell lines and tissue samples from clinical cases. In drug-resistance cell lines, MT expression was studied by immunohistological staining of the avidin -biotin peroxidase complex (ABC) method, and by the radioimmunoassay (RIA) method, using an anti-MT antibody. As for tissue samples from clinical cases, 114 paraffin embedded samples of 29 cases before and after chemotherapy were subjected to immunohistological staining of MT. Human-bladder cancer cell lines with resistance to anticancer drugs (C1-7/CDDP, T-24/ADM) showed increased of expression of MT compared to each parental cell lines (C1-7, T-24), suggesting relationship of resistance to anticancer drugs and MT expression. In the clinical cases, those with continuous administration such as intra-vesicle chemotherapy or oral administration chemotherapy showed greater incidence of positive staining of MT expression in comparison with cases with fewer administrations, such as intra-arterial infusion therapy or intravenous administration chemotherapy. These results demonstrated that repetitive and continuous administration of anticancer drugs cause increase of MT in bladder cancer cell, which may be a possible mechanism of acquired resistance to anticancer drugs.
肿瘤细胞中的金属硫蛋白（MT）已被指出是参与抗癌药物耐药机制的因素之一。利用膀胱癌细胞系和临床病例的组织样本，研究了MT表达与抗癌药物化疗之间的关系。在耐药细胞系中，采用抗MT抗体，通过抗生物素蛋白-生物素过氧化物酶复合物（ABC）法免疫组织化学染色和放射免疫测定（RIA）法研究MT表达。对于临床病例的组织样本，对29例化疗前后的114份石蜡包埋样本进行MT免疫组织化学染色。与各自的亲代细胞系（C1-7、T-24）相比，对抗癌药物耐药的人膀胱癌细胞系（C1-7/顺铂、T-24/阿霉素）MT表达增加，提示抗癌药物耐药性与MT表达有关。在临床病例中，与动脉内灌注治疗或静脉内化疗等给药次数较少的病例相比，膀胱内化疗或口服化疗等持续给药的病例MT表达阳性染色的发生率更高。这些结果表明，重复和持续给予抗癌药物会导致膀胱癌细胞中MT增加，这可能是获得性抗癌药物耐药的一种可能机制。
