维拉帕米对米托蒽醌抗肿瘤活性的增效作用

ENHANCEMENT OF ANTTTUMOR ACTIVITY OF MITOXANTRONE IN HTMAN ACC-2 CELLS IN VITRO AND IN VIVO BY VERAPAMIL

本文利用人唾腺腺样囊性癌ACC-2细胞在体内外研究了钙拮抗剂维拉帕米对米托蒽醌抗癌作用的增效作用。体外实验表明,无毒剂量的维拉帕米与米托蒽醌合用可显著增强对ACC-2细胞的杀伤力,合并用药效果大于二者单用之和,表现为协同作用。~3H—TdR掺入抑制实验发现,米托蒽醌佐以维拉帕米可增强对ACC-2细胞DMA合成的抑制,降低肿瘤细胞的增殖速度。裸鼠体内抑癌实验亦证实了体外实验结果,两药合用明显提高对ACC-2种植瘤的抑瘤率。结果提示有可能将维拉帕米作为米托蒽醌抗癌的增效剂应用于延腺癌的临床化疗。

In this study, the potentiation of Mitoxantrone (DHAD) cytotoxicity by VP was investigated in human adenoid-cystic carcinoma cells (ACC-2) in vitro and in vivo.In vitro studies showed that DHAD combined with nontoxic doses of VP exhibited a synergic cytotoxicity in ACC-2 cells.When 20ug/ml VP was added along with different doses of DHAD to the ACC-2 culture in vitro, the number of cells decreased about 2.8—5.5 fold compared with DHAD single used.~3H-TdR incorperation test indicated that VP enhanced the inhibition of DNA biosynthesis in ACC-2 cells.In vivo studies also proved VP augmented the growth inhibitory effect of DHAD on AGC-2 Xenografts in nude mice.DHAD.at a dose of 2mg/kg, inhibited the tumor growth by 57.9% whereas DHAD combined with VP (50mg/kg) inhibited the tumor growth by 88.4%.These results suggest that VP might be used as an antitumor enhancer of DHAD in clinical chemotherapy trials.