芳香族レチノイン酸誘導体の単独およびマイトマイシンC併用投与によるラット膀胱腫瘍in vitro増殖抑制

Abstract

培養ラット膀胱癌細胞BC50-TCに対するin vitro増殖抑制効果を検討したところ, レチノイドの一種Ro 10-9359, 及びその代謝物Ro 10-1670はともに単独1時間接触では効果がなかったが, 持続接触で増殖抑制効果を示した.MMCは単独1時間接触, 持続接触ともに有効であった.Ro 10-9359またはRo 10-1670とMMCとの併用持続接触では, 相加的ないし高濃度レチノイドでは相乗的効果を示し, 著者ら既報のin vivoにおける効果と対照的であった

The effects of an aromatic retinoic acid analog (Ro 10-9359), its metabolite (Ro 10-1670) and mitomycin C (MMC) on the in vitro growth of rat bladder carcinoma cells, BC50-TC were examined. The growth of the cells treated with 10(-4) M of either of the retinoids for 1 hour was not inhibited. The growth of the cells was inhibited by 37% and 93%, respectively, by the 3-day treatment with Ro 10-9359 and Ro 10-1670, at the concentration of 5 X 10(-5) M. The retinoids given in combination with MMC produced additive effects. Slight synergism was suggested at high concentrations of the retinoid. The fact that the retinoids exhibited anti-tumor activity in vitro might preclude indirect effects from being the only factor in the inhibition of the tumor growth in vivo, but the fact that antagonism with MMC did not occur in vitro whereas it did in vivo suggests that the indirect effects of the retinoid might be more important in mediating the anti-tumor effects. Regardless of the mechanism of action, care should be taken when prescribing retinoids with MMC or other cytotoxic agents.