中药靶向治疗黑色素瘤分子机制研究进展.docVIP

中药靶向治疗黑色素瘤的分子机制研究进展 　　[摘要] 恶性黑色素瘤是一种由于黑素细胞异常增殖引起的皮肤肿瘤，其发病率高、恶性程度高，严重威胁人类健康。恶性黑色素瘤发病早期，可手术切除病灶，但对于中晚期患者的治疗，目前上市的靶向药物均对其不敏感，且易产生耐药性。中药成分复杂，耐药性低，已证实其中含有结构新颖、药理活性显著的先导抗肿瘤成分，这些成分有的能同时或协同作用于多个靶点，使在其中筛选出符合临床要求的多靶点治疗药物成为可能。本文对已发现的抗恶性黑色素瘤中药活性成分及其作用机制进行综述，为开发理想的抗肿瘤药物提供依据。 　　[关键词] 中药；靶向治疗；恶性黑色素瘤；分子机制 　　[中图分类号] R242 [文献标识码] A [文章编号] 1673-7210（2015）08（b）-0029-05 　　`Abstract] Malignant melanoma is a kind of skin tumor which is caused by excessive proliferation of the abnormal melanocytes with an increasing incidence and a high degree of malignancy， it is a serious threat to human health. Treatment for the early stage of malignant melanoma is surgical removal. Nowadays， the targeted drug in market is not sensitive to it and it is easy to develop resistance to other antitumor drugs for the patients who are in the middle-advanced period. The components of Chinese herbs are complicated and the drug resistance of Chinese herbs is low， which has been proved novel structure and leading pharmacological activity of antitumor components exist， these components not only have effect on several targets， but also have synergistic effects on multiple targets. These antitumor components make the screening of multiple targeted drugs meeting the clinical demand possible. This paper reviews the active components of Chinese herbs and molecular mechanism in order to provide the basis for the development of ideal antitumor drugs. 　　[Key words] Chinese medicine； Targeted treatment； Malignant melanoma； Molecular mechanism 　　恶性黑色素瘤是人类皮肤肿瘤中恶性程度较高的肿瘤，多发生于皮肤的黏膜或肢端，极易转移致死。据2012年统计，全球皮肤黑色素瘤新发病例232 130例，死亡55 849例，且其发病率逐年升高。发病早期，首选手术切除，中晚期或高危的早期病变常予以辅助化疗，但其对化疗药物不敏感[1]。随着现代分子生物技术的发展，人类对黑色素瘤发生、发展的分子机制和信号转导途径的认识已逐步深入至分子靶点机制[2]。在恶性黑色素瘤类型中，有丝分裂原活化蛋白激酶（MAPK）通路突变率超过80%，因此，相继出现了有一定疗效并针对MAPK通路的BRAF抑制剂和MEK抑制剂，但这类靶向药物作用时间短，很快会出现耐药，而耐药导致药效降低及肿瘤重新快速生长。中药抗肿瘤有着悠久的历史和丰富的临床经验，多组分、多成分的互相协同可提高疗效，降低毒性，且中药不易产生耐药性。应用现代分子生物技术从调节细胞周期、细胞凋亡、血管新生及与肿瘤发生和发展相关的多个关键性调控靶点开始，发掘结构新颖、药理活性显著、机制相近或相同的先导抗肿瘤中药成分及其可行的协同效应，多靶点抗肿瘤应成为基础和临床研究关注的热点