Inhibition of autophagy induced by TSA sensitizes colon cancer cell to radiation
Inhibition of autophagy induced by TSA sensitizes colon cancer cell to radiation
复制标题
TSA 诱导的自噬抑制使结肠癌细胞对辐射敏感
DOI：
10.1007/s13277-013-1134-z
复制
发表时间：
2014-02-01
期刊：
影响因子：
--
通讯作者：
Zhang, Bo
中科院分区：
文献类型：
--
作者：
He, Gang;Wang, Yan;Zhang, Bo
放射治疗是临床癌症治疗的主要治疗方法之一。然而，由于某些癌症缺乏放射敏感性，其应用受到限制。曲古抑菌素 A (TSA) 是一种经典的组蛋白脱乙酰酶抑制剂 (HDACi)，特异性抑制 HDAC 的生化功能，被证明是一种活性抗癌药物。然而，它是否会使结肠癌对辐射敏感尚不清楚。我们的结果表明，通过 CCK-8 和克隆存活测定确定，TSA 增强了结肠癌细胞的放射敏感性。此外，TSA 治疗增强了辐射诱导的细胞凋亡。此外，TSA还能诱导结肠癌细胞的自噬反应，而自噬抑制则导致细胞凋亡并增强结肠癌细胞的放射敏感性。我们的数据表明，抑制细胞保护性自噬会使癌细胞对辐射敏感，这可能会在临床癌症放射治疗中得到进一步研究。
Radiotherapy is one of the main treatments for clinical cancer therapy. However, its application was limited due to lack of radiosensitivity in some cancers. Trichostatin A (TSA) is a classic histone deacetylases inhibitor (HDACi) that specifically inhibits the biochemical functions of HDAC and is demonstrated to be an active anticancer drug. However, whether it could sensitize colon cancer to radiation is not clear. Our results showed that TSA enhanced the radiosensitivity of colon cancer cells as determined by CCK-8 and clonogenic survival assay. Moreover, apoptotic cell death induced by radiation was enhanced by TSA treatment. Additionally, TSA also induced autophagic response in colon cancer cells, while autophagy inhibition led to cell apoptosis and enhanced the radiosensitivity of colon cancer cells. Our data suggested that inhibition of cytoprotective autophagy sensitizes cancer cell to radiation, which might be further investigated for clinical cancer radiotherapy.