Department of Plastic Surgery, Changzheng Hospital, 18F, No, 415 Fengyang Road, Shanghai, China.
Cancer Cell Int. 2014 Feb 25;14(1):16. doi: 10.1186/1475-2867-14-16.
Liver X receptors (LXRs) are nuclear receptors that function as ligand-activated transcription factors regulating lipid metabolism and inflammation. Recent discoveries found LXRs could regulate tumor growth in a variety of cancer cell lines. In this study, we investigated the effect of LXR activation on melanoma cell proliferation and apoptosis both in vitro and in vivo. Treatment of B16F10 and A-375 melanoma cells with synthetic LXR agonist T0901317 significantly inhibited the proliferation of melanoma cells in vitro. Meanwhile, T0901317 induced the apoptosis of B16F10 melanoma cells in a dose-dependent manner. Furthermore, western blot assay showed that the pro-apoptotic effect of T0901317 on B16F10 melanoma cells was mediated through caspase-3 pathway. Oral administration of T0901317 inhibited the growth of B16F10 melanoma in C56BL/6 mice. Altogether, this study demonstrates the critical role of LXRs in the regulation of melanoma growth and presents the LXR agonist T0901317 as a potential anti-melanoma agent.
肝 X 受体 (LXRs) 是核受体，作为配体激活的转录因子，调节脂质代谢和炎症。最近的发现表明，LXRs 可以调节多种癌细胞系中的肿瘤生长。在这项研究中，我们研究了 LXR 激活对体外和体内黑素瘤细胞增殖和凋亡的影响。用合成 LXR 激动剂 T0901317 处理 B16F10 和 A-375 黑素瘤细胞，显著抑制了黑素瘤细胞在体外的增殖。同时，T0901317 以剂量依赖的方式诱导 B16F10 黑素瘤细胞凋亡。此外，Western blot 分析表明，T0901317 对 B16F10 黑素瘤细胞的促凋亡作用是通过半胱天冬酶-3 途径介导的。T0901317 的口服给药抑制了 C56BL/6 小鼠中 B16F10 黑素瘤的生长。总之，这项研究表明 LXRs 在调节黑素瘤生长中起关键作用，并提出 LXR 激动剂 T0901317 可能是一种潜在的抗黑素瘤药物。
