Schadendorf D, Herfordt R, Czarnetzki B M
University Hospital Rudolf Virchow, Department of Dermatology, FU Berlin, Germany.
Br J Dermatol. 1995 Apr;132(4):551-5. doi: 10.1111/j.1365-2133.1995.tb08710.x.
Metastatic malignant melanoma is notoriously resistant to chemotherapeutic agents, but the exact mechanisms involved in this drug resistance are unknown. One recently defined major mechanism of multidrug resistance involves the overexpression of P-glycoprotein on cell membranes. In order to evaluate the significance of this putative drug efflux pump for chemoresistance of malignant melanoma, five different antibodies were employed to examine P-glycoprotein expression on tissue from 33 primary malignant melanomas and 35 metastases, before and after chemotherapy, using immunohistological techniques. The expression of P-glycoprotein was low on primary cutaneous melanomas (three of 33), and on metastases (one of 35). Normal tissue in and around the melanoma showed reactivity of endothelial cells, stromal cells and eccrine sweat glands with several antibodies tested. Chemotherapy with drugs commonly used in metastatic melanoma, including agents known to induce P-glycoprotein expression in other tumours (vindesine, cisplatin) had no effect on P-glycoprotein expression in human melanoma metastases. The high chemoresistance of human melanoma cells in vitro and in vivo is probably not mediated via P-glycoprotein, and other possible mechanisms involved will have to be explored in future studies.
转移性恶性黑色素瘤对化疗药物具有众所周知的耐药性，但其耐药的确切机制尚不清楚。最近确定的多药耐药的一个主要机制涉及细胞膜上P-糖蛋白的过度表达。为了评估这种假定的药物外排泵对恶性黑色素瘤化疗耐药性的意义，使用五种不同的抗体，采用免疫组织学技术，检测33例原发性恶性黑色素瘤和35例转移灶化疗前后组织中P-糖蛋白的表达。原发性皮肤黑色素瘤（33例中的3例）和转移灶（35例中的1例）中P-糖蛋白的表达较低。黑色素瘤及其周围的正常组织显示，内皮细胞、基质细胞和外分泌汗腺对几种测试抗体有反应。用转移性黑色素瘤常用的药物进行化疗，包括已知能在其他肿瘤中诱导P-糖蛋白表达的药物（长春地辛、顺铂），对人黑色素瘤转移灶中P-糖蛋白的表达没有影响。人黑色素瘤细胞在体外和体内的高化疗耐药性可能不是通过P-糖蛋白介导的，未来的研究将不得不探索其他可能涉及的机制。
