The chemoresistance of human malignant melanoma: an update
The chemoresistance of human malignant melanoma: an update
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DOI：
10.1097/00008390-199902000-00007
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发表时间：
1999-02-01
影响因子：
2.2
通讯作者：
Horsey, P
中科院分区：
文献类型：
--
作者：
Serrone, L;Horsey, P
恶性黑色素瘤被认为是一种化疗难治性肿瘤，常用的抗癌药物似乎不能改变转移性疾病的预后。涉及黑色素瘤化疗耐药的细胞耐药机制尚未阐明。黑素瘤衍生的细胞系通常具有显著的化学抗性。使用体外软琼脂培养系统预测肿瘤细胞的敏感性，在良好建立的人黑色素瘤细胞系，对所有的细胞生长抑制剂的高度耐药性研究已被报道，这表明存在内在的细胞耐药机制。P-糖蛋白，多药耐药相关蛋白（MRP），谷胱甘肽/谷胱甘肽S-转移酶系统和拓扑异构酶II酶介导的明确的耐药机制的相关性进行了审查。突变的N-Ras癌基因最近被牵连在黑色素瘤耐顺铂，在体外和体内，和其他两个癌基因，Bcl-2和p53，这是已经参与血液和实体恶性肿瘤的化疗耐药性的作用，开始得到更好的阐明。许多化疗药物可以通过凋亡途径杀死敏感细胞，这一发现为化疗耐药机制提供了新的分子见解，并表明应研究黑色素瘤细胞的凋亡和/或抗凋亡，以更好地阐明黑色素瘤化疗耐药的机制。(C)1999年利平科特威廉姆斯&威尔金斯。
Malignant melanoma is considered to be a chemotherapy-refractory tumour and the commonly used anticancer drugs do not seem to modify the prognosis of metastatic disease. The cellular resistance mechanisms involved in melanoma chemoresistance have not yet been elucidated. Melanoma-derived cell lines are often markedly chemoresistant. Using the in vitro soft agar culture system to predict tumour cell sensitivity in well-established human melanoma cell lines, a high degree of resistance against all the cytostatic agents studied has been reported, suggesting the presence of intrinsic cellular resistance mechanisms. The relevance of the well-defined resistance mechanisms mediated by P-glycoprotein, multidrug resistance-associated protein (MRP), the glutathione/glutathione S-transferase system and topoisomerase II enzyme are reviewed. Mutated N-Ras oncogene has recently been implicated in melanoma resistance to cisplatin, both in vitro and in vivo, and the role of two other oncogenes, Bcl-2 and p53, which are already involved in the chemoresistance of haematological and solid malignancies, is beginning to be better elucidated. The finding that many chemotherapeutic agents can kill susceptible cells through the apoptosis pathway provides new molecular insight into chemoresistance mechanisms and suggests that apoptosis and/or resistance to apoptosis of melanoma cells should be investigated to better clarify the mechanism of melanoma chemoresistance. (C) 1999 Lippincott Williams & Wilkins.