Onoda J M, Jacobs J R, Taylor J D, Sloane B F, Honn K V
Cancer Lett. 1986 Feb;30(2):181-8. doi: 10.1016/0304-3835(86)90087-x.
Calcium channel blockers of 3 chemical classes and calmodulin antagonists have recently been shown to enhance the cytotoxicity of conventional cancer chemotherapeutic agents. We tested the ability of nifedipine, a dihydropyridine class calcium channel blocker, to enhance the cytotoxicity of cisplatin, the current chemotherapeutic of choice against human head and neck tumors and testicular carcinoma. Both in vitro and in vivo, combination therapy with nifedipine and cisplatin resulted in synergistic inhibition of tumor cell proliferation, primary tumor growth and appearance of spontaneous pulmonary metastases. This combination also significantly increased the survival of mice bearing cisplatin-resistant tumors. This is the first indication that calcium channel blockers can enhance the cytotoxicity of cisplatin as well as the first demonstration that calcium channel blockers can enhance cytotoxicity of chemo-therapeutic agent against a solid tumor and its metastases.
最近研究表明，3种化学类别的钙通道阻滞剂和钙调蛋白拮抗剂可增强传统癌症化疗药物的细胞毒性。我们测试了二氢吡啶类钙通道阻滞剂硝苯地平增强顺铂细胞毒性的能力，顺铂是目前治疗人类头颈肿瘤和睾丸癌的首选化疗药物。无论是在体外还是体内，硝苯地平和顺铂联合治疗均能协同抑制肿瘤细胞增殖、原发性肿瘤生长以及自发性肺转移的出现。这种联合治疗还显著提高了携带顺铂耐药肿瘤小鼠的生存率。这首次表明钙通道阻滞剂可增强顺铂的细胞毒性，也是首次证明钙通道阻滞剂可增强化疗药物对实体瘤及其转移灶的细胞毒性。
