Retinoid receptors are a family of intracellular hormone receptors consisting of retinoic acid receptors (RARs) and retinoid X receptors (RXRs). Bexarotene is a selective activator of RXRs with EC50 values of 28, 25, and 20 nM for RXRa, b, and g, respectively[5]. In BEAS-2B cells, 1 µM bexarotene remarkably promoted UBE1L immunoblot expression 10 days following the treatment compared to vehicle-treated cells. Bexarotene treatment (0.05 – 0.5 µM) also dose-dependently inhibited BEAS-2B clonal growth[6]. In Sprague-Dawley rats with NMU-induced tumors, daily administration of bexarotene (p.o., 100 mg/kg) for 6 weeks significantly suppressed tumor growth compared to vehicle-treated group. Bexarotene at 100 mg/kg completed regressed 72.2% of the primary tumors and partially suppressed 16.7% of the tumors. Administration of bexarotene at 10 and 30 mg/kg also showed anti-tumor efficacy with 10.5% and 27.8%, respectively, of tumors completely regressing. Compared to vehicle-administered control rats, bexarotene-treated animals showed decreased tumor burden at a dose-dependent manner with the values of 376, 121, and 95 mm2 at 10, 30, and 100 mg/kg, respectively. Moreover, bexarotene treatment (100 mg/kg) significantly reduced cellular proliferation index in the NMU-induced rat mammary carcinoma model[7].
作用机制
Bexarotene is a synthetic high-affinity ligand for RXRs that activates the dimerization of RXR and its partner to regulate gene expression[5].
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