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贝林司他(PXD101)抵抗 UVB 照射诱导的细胞衰老和皮肤光老化。

Belinostat (PXD101) resists UVB irradiation-induced cellular senescence and skin photoaging.

机构信息

School of Basic Medicine, Dali University, Dali, Yunnan, 671000, China; Key Laboratory of University Cell Biology Yunnan Province, Dali, Yunnan, 671000, China.

School of Basic Medicine, Dali University, Dali, Yunnan, 671000, China.

出版信息

Biochem Biophys Res Commun. 2022 Oct 30;627:122-129. doi: 10.1016/j.bbrc.2022.08.038. Epub 2022 Aug 17.

Abstract

Belinostat (PXD101), a new histone deacetylase inhibitor, has shown good performance in various cancer treatments and has been approved by the FDA for the treatment of recurrent or refractory peripheral T-cell lymphoma (PTCL) in patients with drugs. PXD101 is considered to have certain anti-allergic and anti-inflammatory properties, but its beneficial effects in UVB-induced skin photoaging have not been reported. In a recent study, HacaT cells and C57BL6 mice were used to study the impact of PXD101 on UVB-induced cellular senescence and skin photoaging and to explore their potential mechanisms of action. Studies have shown that PXD101 inhibits UVB-induced HacaT cell senescence, which appears to be achieved by inhibiting activation of the UVB-induced NF-κB/p65 signaling pathway. At the same time, PXD101 inhibits the expression of MMPs. In addition, PXD101 alleviated skin damage on the dorsal skin of mice, reduced skin aging and inflammation, increased collagen fiber synthesis, and restored UVB-induced epidermal thickening. In short, we believe that PXD101 effectively inhibits cellular senescence and skin photoaging caused by UVB exposure, a potential method for developing clinical prevention and treatment of skin aging.

摘要

贝林司他(PXD101),一种新型组蛋白去乙酰化酶抑制剂,在多种癌症治疗中表现出色,已被 FDA 批准用于治疗药物难治或复发性外周 T 细胞淋巴瘤(PTCL)。PXD101 被认为具有一定的抗过敏和抗炎特性,但尚未有报道称其对 UVB 诱导的皮肤光老化具有有益作用。在最近的一项研究中,使用 HacaT 细胞和 C57BL6 小鼠研究了 PXD101 对 UVB 诱导的细胞衰老和皮肤光老化的影响,并探讨了其潜在的作用机制。研究表明,PXD101 抑制了 UVB 诱导的 HacaT 细胞衰老,这似乎是通过抑制 UVB 诱导的 NF-κB/p65 信号通路的激活来实现的。同时,PXD101 抑制了 MMPs 的表达。此外,PXD101 减轻了小鼠背部皮肤的损伤,减少了皮肤衰老和炎症,增加了胶原蛋白纤维的合成,并恢复了 UVB 诱导的表皮增厚。总之,我们认为 PXD101 能有效抑制 UVB 暴露引起的细胞衰老和皮肤光老化,为开发皮肤衰老的临床预防和治疗方法提供了一种潜在的方法。

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