Sirtuin-3 (SIRT3), a novel potential therapeutic target for oral cancer.
Sirtuin-3 (SIRT3), a novel potential therapeutic target for oral cancer.
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DOI：
10.1002/cncr.25676
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发表时间：
2011-04-15
期刊：
影响因子：
6.2
通讯作者：
Kapila, Yvonne L.
中科院分区：
文献类型：
--
作者：
Alhazzazi, Turki Y.;Kamarajan, Pachiyappan;Joo, Nam;Huang, Jing-Yi;Verdin, Eric;D'Silva, Nisha J.;Kapila, Yvonne L.
sirtuin家族的几个成员（SIRT 1 -7），是进化上保守的NAD依赖性脱乙酰酶，在肿瘤发生中起着重要作用。然而，它们在口腔癌中的作用尚未被研究。因此，本研究的目的是调查sirtuins是否在口腔癌的致癌作用。将几种口腔鳞状细胞癌（OSCC）细胞系中所有sirtuins的表达水平与正常人口腔角质形成细胞进行比较，并观察到SIRT 3高表达。因此，使用组织微阵列来评估这种过表达的临床相关性。通过细胞增殖和细胞活力测定研究和分析SIRT 3在OSCC细胞增殖和存活中的下调。用电离辐射和顺铂研究SIRT 3下调是否能增加OSCC对两种治疗的敏感性。为了进一步评估SIRT 3在OSCC致癌作用中的体内作用，使用口底口腔癌小鼠模型来研究SIRT 3下调对免疫缺陷小鼠中OSCC肿瘤生长的影响。目前的研究结果首次证明，SIRT 3在体外和体内OSCC中与其他sirtuins相比过表达。SIRT 3的下调抑制了OSCC细胞的生长和增殖，并增加了OSCC细胞对体外放射和顺铂治疗的敏感性。SIRT 3下调也降低了体内肿瘤负荷。目前的研究揭示了SIRT 3在口腔癌癌变中作为细胞增殖和存活的促进剂的新作用，从而暗示SIRT 3作为治疗口腔癌的新的潜在治疗靶点。癌症2011年。© 2010美国癌症协会。
Several sirtuin family members (SIRT1-7), which are evolutionarily conserved NAD-dependent deacetylases, play an important role in carcinogenesis. However, their role in oral cancer has not yet been investigated. Therefore, the objective of this study was to investigate whether sirtuins play a role in oral cancer carcinogenesis. The expression levels of all sirtuins in several oral squamous cell carcinoma (OSCC) cell lines were compared with normal human oral keratinocytes and observed that SIRT3 was highly expressed. Therefore, tissue microarrays were used to evaluate the clinical relevance of this overexpression. SIRT3 down-regulation in OSCC cell proliferation and survival was investigated and analyzed by using cell-proliferation and cell-viability assays. Ionizing radiation and cisplatin were used to investigate whether SIRT3 down-regulation could increase the sensitivity of OSCC to both treatments. To further assess the in vivo role of SIRT3 in OSCC carcinogenesis, a floor-of-mouth oral cancer murine model was used to study the effect of SIRT3 down-regulation on OSCC tumor growth in immunodeficient mice. The current results demonstrated for the first time that SIRT3 is overexpressed in OSCC in vitro and in vivo compared with other sirtuins. Down-regulation of SIRT3 inhibited OSCC cell growth and proliferation and increased OSCC cell sensitivity to radiation and cisplatin treatments in vitro. SIRT3 down-regulation also reduced tumor burden in vivo. The current investigation revealed a novel role for SIRT3 in oral cancer carcinogenesis as a promoter of cell proliferation and survival, thus implicating SIRT3 as a new potential therapeutic target to treat oral cancer. Cancer 2011. © 2010 American Cancer Society.
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