[Verapamil enhancement of antitumor effect of mitoxantrone on ACC-2 cell line in vitro and in vivo].

In this study, we investigated the effects of combination of Ca++ antagonist verapamil (VP) with a new anticancer agent, mitoxantrone (DHAD) on the growth of human adenoid cystic carcinoma cell (ACC-2) in vitro and in vivo. Non-toxic VP enhanced the cytotoxicity of DHAD in ACC-2 cells and significantly inhibited the cell proliferation. VP potentiated DHAD's inhibitory effect on incorporation of 3H-TdR into ACC-2 cells. When combined use of VP with DHAD, IC50 of DHAD on DNA synthesis decreased by 3.32 fold. FCM analysis showed that VP enhanced the block effect of DHAD on ACC-2 cell cycle traverse, causing cell accumulation in the G2M phase. In vivo study also proved that VP enhanced the tumoricidal effect of DHAD on ACC-2 implanted to nude mice. The inhibitory rate of tumor growth was increased from 57.9% to 88.4% when DHAD was administered with VP.