TSA对非小细胞肺癌A549细胞放疗增敏性的研究

Radiosensitizing effect of trichostatin A (TSA) on non-small cell lung cancer A549 cells

目的:探讨组蛋白去乙酰化酶抑制剂(HDIs)trichostatin A(TSA)对非小细胞肺癌(NSCLC)A549细胞放疗敏感性的影响。方法:以5Gy γ-射线照射细胞,或同时以TSA处理细胞。采用MTT法检测细胞存活率,Annexin V-PI染色检测细胞凋亡,流式细胞仪检测caspase-3活性。结果:5Gy γ-射线可轻度降低细胞存活率,仅有少量细胞发生凋亡,但同时以TSA和γ-射线处理细胞,细胞存活率明显下降,凋亡细胞显著增多,且明显提高活化的caspase-3水平。结论:TSA通过促进caspase-3激活增强A549细胞对γ-射线的敏感性。

Objective： To define the activity of trichostatin A （TSA）, one of the HDIs, to radiosensitize human non-small cell lung cancer （NSCLC） cell line A549 cells in vitro. Methods： A549 cells were exposed to N-irradiation with or without TSA co-treatment. MTT assay was performed to evaluate cell viability. Apoptosis was analyzed with Annexin V-PI staining by flow cytometry. Active form of caspase-3 positive cells was measured by flow cytometry. Results： The results showed that co-treatment of TSA 1μM significantly radiosensitized A549 cells to N-irradiation （5Gy） by decreasing cell viability. γ-irradiation or TSA alone caused only a small amount of apoptotic cells, as indicated by Annexin V positive cells. However, TSA co-treatment significantly enhanced γ-irradiation-induced apop- tosis. Meanwhile, in TSA and N-irradiation co-treatment group, cells positive for caspase-3 active form were significantly increased compared to group treated with N-irradiation （5Gy） or TSA alone. Conclusions： Taken together, these results suggest that TSA has potential to act as radio-sensitizer in A549 cells by promoting caspase-3 activity and increasing apoptosis.