一种新型的沉默调节蛋白-3抑制剂LC-0296可抑制头颈部癌细胞的存活和增殖，并促进其凋亡。
A Novel Sirtuin-3 Inhibitor, LC-0296, Inhibits Cell Survival and Proliferation, and Promotes Apoptosis of Head and Neck Cancer Cells.
作者信息
Alhazzazi Turki Y, Kamarajan Pachiyappan, Xu Yanli, Ai Teng, Chen Liqiang, Verdin Eric, Kapila Yvonne L
机构信息
Department of Oral Biology, King Abdulaziz University, Faculty of Dentistry, Jeddah, Saudi Arabia Department of Periodontics and Oral Medicine, School of Dentistry, University of Michigan, Ann Arbor, MI, U.S.A.
Department of Periodontics and Oral Medicine, School of Dentistry, University of Michigan, Ann Arbor, MI, U.S.A.
出版信息
Anticancer Res. 2016 Jan;36(1):49-60.
BACKGROUND
The survival rate of patients with head and neck squamous cell carcinoma (HNSCC) stands at approximately 50% and this has not improved in decades. This study developed a novel sirtuin-3 (SIRT3) inhibitor (LC-0296) and examined its role in altering HNSCC tumorigenesis.
MATERIALS AND METHODS
The effect of the SIRT3 inhibitor, LC-0296, on cell survival, proliferation, and apoptosis, and reactive oxygen species levels in HNSCC cells were studied.
RESULTS
LC-0296 reduces cell proliferation and promotes apoptosis of HNSCC cells but not of normal human oral keratinocytes. This inhibitory effect is mediated, in part, via modulation of reactive oxygen species levels. Additionally, LC-0296 works synergistically to increase the sensitivity of HNSCC cells to radiation and cisplatin treatment.
CONCLUSION
Development of novel SIRT3 inhibitors, such as LC-0296, might enable the development of new targeted therapies to treat and improve the survival rate of patients with head and neck cancer.
背景
头颈部鳞状细胞癌（HNSCC）患者的生存率约为50%，且几十年来一直没有提高。本研究开发了一种新型的沉默调节蛋白3（SIRT3）抑制剂（LC - 0296），并研究了其在改变HNSCC肿瘤发生过程中的作用。
材料与方法
研究了SIRT3抑制剂LC - 0296对HNSCC细胞的细胞存活、增殖、凋亡及活性氧水平的影响。
结果
LC - 0296可降低HNSCC细胞的增殖并促进其凋亡，但对正常人口腔角质形成细胞无此作用。这种抑制作用部分是通过调节活性氧水平介导的。此外，LC - 0296协同作用可增加HNSCC细胞对放疗和顺铂治疗的敏感性。
结论
开发新型SIRT3抑制剂，如LC - 0296，可能有助于开发新的靶向治疗方法来治疗头颈部癌并提高患者生存率。
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