Institute of Toxicology, College of Medicine, National Taiwan University, Taipei, Taiwan.
Department of Surgery, National Taiwan University Hospital Hsin-Chu Branch, Hsin-Chu, Taiwan.
Sci Rep. 2017 Jun 9;7(1):3180. doi: 10.1038/s41598-017-03635-7.
Chondrosarcoma is a malignant primary bone tumor. Sirtuin-1 (SIRT1), which is a member of sirtuin family, plays a dual role either in cancer promotion or suppression. There is no report about the role of SIRT1 in the human chondrosarcoma cells. Resveratrol is a potent activator of SIRT1. However, its effects on chondrosarcoma have not been extensively studied. Here, we investigated the role of SIRT1 induction by resveratrol in human chondrosarcoma cell growth and tumor progression. Resveratrol significantly decreased cell viability and induced cell apoptosis in human chondrosarcoma cells in a dose-dependent manner. The protein expression and activity of SIRT1 were activated after treatment with resveratrol. Resveratrol significantly inhibited NF-κB signaling by deacetylating the p65 subunit of NF-κB complex, which could be reversed by siRNA-SIRT1 transfection or deacetylation inhibitor MS-275. Resveratrol induced-apoptosis involved a caspase-3-mediated mechanism. Both siRNA-SIRT1 transfection and MS-275 significantly inhibited the resveratrol-induced caspase-3 cleavage and activity in human chondrosarcoma cells. Moreover, in vivo chondrosarcoma xenograft study revealed a dramatic reduction in tumor volume and the increased SIRT1 and cleaved caspase-3 expressions in tumors by resveratrol treatment. These results suggest that resveratrol induces chondrosarcoma cell apoptosis via a SIRT1-activated NF-κB deacetylation and exhibits anti-chondrosarcoma activity in vivo.
软骨肉瘤是一种恶性原发性骨肿瘤。Sirtuin-1（SIRT1）是 Sirtuin 家族的成员，在癌症的促进或抑制中发挥双重作用。目前尚无关于 SIRT1 在人软骨肉瘤细胞中的作用的报道。白藜芦醇是 SIRT1 的有效激活剂。然而，其对软骨肉瘤的影响尚未得到广泛研究。在这里，我们研究了白藜芦醇诱导的 SIRT1 对人软骨肉瘤细胞生长和肿瘤进展的作用。白藜芦醇以剂量依赖的方式显著降低人软骨肉瘤细胞的活力并诱导细胞凋亡。白藜芦醇处理后 SIRT1 的蛋白表达和活性被激活。白藜芦醇通过去乙酰化 NF-κB 复合物的 p65 亚基显著抑制 NF-κB 信号，该作用可被 siRNA-SIRT1 转染或去乙酰化抑制剂 MS-275 逆转。白藜芦醇诱导的细胞凋亡涉及 caspase-3 介导的机制。siRNA-SIRT1 转染和 MS-275 均可显著抑制人软骨肉瘤细胞中白藜芦醇诱导的 caspase-3 切割和活性。此外，体内软骨肉瘤异种移植研究表明，白藜芦醇处理可显著降低肿瘤体积，并增加肿瘤中 SIRT1 和切割的 caspase-3 的表达。这些结果表明，白藜芦醇通过 SIRT1 激活的 NF-κB 去乙酰化诱导软骨肉瘤细胞凋亡，并在体内表现出抗软骨肉瘤活性。
