Chen Yuting, Chen Jiajia, Yun Lin, Xu Longmei, Liu Jiaxian, Xu Yongchun, Yang Hui, Liang Hairong, Tang Huanwen
School of Public Health, Guangdong Medical University, PR-523808 Dongguan, Guangdong, China; Dongguan Key Laboratory of Enviromental Medicine, PR-523808 Dongguan, Guangdong, China.
School of Public Health, Guangdong Medical University, PR-523808 Dongguan, Guangdong, China; Dongguan Key Laboratory of Enviromental Medicine, PR-523808 Dongguan, Guangdong, China.
Toxicol Lett. 2016 Sep 30;259:133-142. doi: 10.1016/j.toxlet.2016.08.006. Epub 2016 Aug 8.
Hydroquinone (HQ), known as one of the metabolic products of benzene, causes a number of hematologic malignancies. The study evaluated the potential mechanism of Sirtuin 1 (SIRT1) in HQ-induced TK6 cell malignant transformation. The data of our study show that short term exposure of TK6 cells to HQ led to a decrease expression of SIRT1. Knockdown of SIRT1 sensitized to the HQ-induced apoptosis in vitro and increased the expression of p53, p21 and γ-H2AX. Furthermore, chronic HQ-treated (20μM once a week for 19 weeks) caused carcinogenic transformation and was confirmed by abnormal cell proliferation, matrix metalloproteinase 9(MMP9) and subcutaneous tumor formation in nude mice. SIRT1 increased KRAS expression, and decreased H3K9 and H3K18 acetylation, inhibited p53 signaling and the level of caspase-3 in HQ-induced transformation cells. Taken together, these data suggest that SIRT1 is involved in HQ-induced malignant transformation associated with suppressing p53 signaling and activation of KRAS.
对苯二酚（HQ）是苯的代谢产物之一，可引发多种血液系统恶性肿瘤。本研究评估了沉默调节蛋白1（SIRT1）在HQ诱导的TK6细胞恶性转化中的潜在机制。我们的研究数据表明，TK6细胞短期暴露于HQ会导致SIRT1表达降低。敲低SIRT1可使细胞对HQ诱导的体外凋亡敏感，并增加p53、p21和γ-H2AX的表达。此外，长期HQ处理（每周一次20μM，共19周）会导致致癌转化，这在裸鼠体内通过异常细胞增殖、基质金属蛋白酶9（MMP9）和皮下肿瘤形成得到证实。SIRT1增加KRAS表达，降低H3K9和H3K18乙酰化水平，抑制HQ诱导的转化细胞中的p53信号通路和半胱天冬酶-3水平。综上所述，这些数据表明SIRT1参与了HQ诱导的与抑制p53信号通路和激活KRAS相关的恶性转化。
