薬理と治療

Abstract

Bexarotene has been used for the clinical treatment of cutaneous T-cell lymphoma （CTCL）in many countries. Though this FDA︱approved selective RXR agonist is known to inhibit the proliferation of CTCL cells in culture, the anti-tumor effect of bexarotene have not been investigated in CTCL-animal models. In this study, we examined the inhibitory effect of bexarotene on cell growth of variant cells derived from patients with CTCL in vitro and tumor progression in CTCT cell-xenografted mice. Bexarotene inhibited the proliferation of HuT 78 and HH cells but not MJ cells with a double-sigmoid curve. Tumor progression in HH cell-xenografted mice was significantly suppressed from day 11 to day 28 by daily oral treatment with bexarotene at 30 mg/kg or 100 mg/kg. In addition, bexarotene significantly upregulated the expression of mRNA encoding p21 but not Rb in tumor after 2 weeks. Furthermore, the mRNA for RXRα in tumor was markedly induced by bexarotene at 100 mg╱kg after 2 weeks. Bexarotene also enhanced the expression of RXRα protein after 2 and 4 weeks. 　　We have demonstrated for the first time that bexarotene treatment can inhibit tumor growth in a CTCL animal model, and suggest that the mechanism may involve upregulation of RXRα and╱or p21 expression.