Onoda J M, Nelson K K, Pilarski S M, White N S, Mihu R G, Honn K V
Department of Radiation Oncology, Wayne State University, Detroit, Michigan.
Clin Exp Metastasis. 1990 Jan-Feb;8(1):59-73. doi: 10.1007/BF00155593.
Cisplatin has become one of the most commonly prescribed cytotoxic chemotherapeutic agents. Unfortunately, the cure rate is low due to the development or outgrowth of cisplatin-resistant cells which repopulate tumors, resulting in patient death. We reported previously that the calcium channel blocker nifedipine enhances the antitumour actions of cisplatin (cis-diamminedichloroplatinum (II] against murine tumors which are inherently cisplatin-sensitive (B16a) or inherently cisplatin-resistant (3LL). We have developed an induced cisplatin-resistant tumor variant (B16a-Pt) that is 30 times more resistant to cisplatin than its cisplatin-sensitive parent line. In short-term studies, we report that nifedipine significantly enhanced the cytotoxicity of cisplatin against primary B16a-Pt tumors and their spontaneous pulmonary metastases. In long term studies, we report that combination therapy with nifedipine and cisplatin results in significantly enhanced survival.
顺铂已成为最常用的细胞毒性化疗药物之一。不幸的是，由于顺铂耐药细胞的发展或生长，导致肿瘤重新增殖，治愈率较低，最终导致患者死亡。我们之前报道过，钙通道阻滞剂硝苯地平可增强顺铂（顺二氨二氯铂（II））对固有顺铂敏感（B16a）或固有顺铂耐药（3LL）的小鼠肿瘤的抗肿瘤作用。我们已经培育出一种诱导性顺铂耐药肿瘤变体（B16a-Pt），其对顺铂的耐药性是其顺铂敏感亲代细胞系的30倍。在短期研究中，我们发现硝苯地平显著增强了顺铂对原发性B16a-Pt肿瘤及其自发性肺转移瘤的细胞毒性。在长期研究中，我们发现硝苯地平和顺铂联合治疗可显著提高生存率。
