[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.
Chen
J W
JW
School of Stomatology, Shanghai Second Medical University.
Qiu
W L
WL
He
R G
RG
D000818:Animals; D003528:Carcinoma, Adenoid Cystic / Q000188:drug therapy* / Q000473:pathology; D004273:DNA, Neoplasm / Q000096:biosynthesis; D004357:Drug Synergism; D005260:Female; D006801:Humans; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D008942:Mitoxantrone / Q000494:pharmacology* / Q000627:therapeutic use; D009368:Neoplasm Transplantation; D012468:Salivary Gland Neoplasms / Q000188:drug therapy* / Q000473:pathology; D012470:Salivary Glands, Minor; D014407:Tumor Cells, Cultured; D014700:Verapamil / Q000494:pharmacology* / Q000627:therapeutic use
D004273:DNA, Neoplasm; D008942:Mitoxantrone; D014700:Verapamil