Potentiation of the cytotoxicity of carboquone by flavone acetic acid combined with hyperthermia

Hideya Takeuchi, Hideo Baba, Sadaaki Inutsuka, Yoshihiko Maehara, Keizo Sugimachi

研究成果: ジャーナルへの寄稿学術誌査読

3 被引用数 (Scopus)

抄録

Flavone acetic acid (FAA) has shown the effectiveness of vasoactive drugs in the selective reduction of tumor blood flow. A FAA-mediated decrease in tumor blood flow may produce sufficient hypoxic conditions within the tumor. Carboquone (CQ), a naturally occurring prototype bioreductive alkylating agent like mitomycin C (MMC), has been shown to be selectively more cytotoxic toward hypoxic tumor cells. We have reported enhancement of the combined antitumor effects of MMC plus FAA and hyperthermia (HT). In this study, we examined the combined effects of FAA, CQ and HT. In vitro, although HT (43°C, 60 min) reduced the colonogenicity to 0.58 in CQ (0.01 μg/ml) alone, the combined cytotoxicity of CQ and HT was not enhanced with exposure to FAA at a concentration of 100 μg/ml. In vivo, the tumor growth time, calculated as the time required to reach twice the initial tumor volume, for CQ (2 mg/kg) alone, FAA (150 mg/kg) alone, CQ+FAA, CQ+HT (43°C, 15 min), FAA+HT and FAA+CQ+HT was 6.1, 5.1, 7.1, 8.0, 7.6 and 13.4 days, respectively. A significant enhancement of antitumor effects by trimodality therapy with CQ, FAA and HT was observed, when compared to the treatment with CQ and FAA (p < 0.05). The possible mechanisms of an increased antitumor response achieved with the combination of CQ, FAA and HT may be explained in the following way: the FAA-mediated decrease in tumor blood flow produced sufficient hypoxic conditions within the tumor, and these resulted in a significant increase of the antitumor effects of CQ and HT.

本文言語英語
ページ(範囲)778-783
ページ数6
ジャーナルAnti-cancer drugs
8
8
DOI
出版ステータス出版済み - 11月 1 1997

!!!All Science Journal Classification (ASJC) codes

  • 腫瘍学
  • 薬理学
  • 薬理学(医学)
  • 癌研究

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