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目的:探讨组蛋白去乙酰化酶抑制剂(histone deacetylase inhibitor,HDACI)曲古抑霉素A(trichostatin A,TSA)对体外培养的骨肉瘤MNNG/HOS细胞凋亡的影响。方法:用50、100、200、300和500nmol/L TSA分别作用体外培养的骨肉瘤MNNG/HOS细胞12、24和48h,在透射电子显微镜下观察细胞形态学变化,应用MTT、FCM和TUNEL法检测TSA对骨肉瘤细胞增殖、细胞周期和细胞凋亡的影响。结果:TSA具有抑制骨肉瘤MNNG/HOS细胞增殖的作用,并且随着TSA浓度的增加和作用时间的延长而增强(P<0.01)。FCM检测结果显示,与对照组比较,300nmol/L TSA作用组G1期细胞减少,G2/M期细胞增加,细胞凋亡率增加,差异有统计学意义(P<0.05)。TUNEL法检测结果显示,细胞凋亡指数随着TSA浓度的增加和作用时间的延长而上升,与对照组比较差异有统计学意义(P<0.05)。透射电子显微镜下观察发现,TSA作用后,凋亡的骨肉瘤细胞细胞质浓缩,并可见凋亡小体。结论:TSA可抑制体外培养的骨肉瘤MNNG/HOS细胞增殖并诱导其凋亡,可能与G2/M期细胞周期阻滞有关。HDACI可能成为一种新的骨肉瘤治疗策略及抗肿瘤药物。
Objective: To investigate the effect of histone deacetylase inhibitor (HDACI) trichostatin A (TSA) on the apoptosis of MNNG / HOS cells in vitro. METHODS: MNNG / HOS cells were treated with 50, 100, 200, 300 and 500 nmol / L TSA for 12, 24 and 48 h respectively. Morphological changes were observed under transmission electron microscope. MTT, FCM and TUNEL The effect of TSA on the proliferation, cell cycle and apoptosis of osteosarcoma cells was detected. Results: TSA could inhibit the proliferation of osteosarcoma MNNG / HOS cells, and increased with the increase of TSA concentration and time (P <0.01). Compared with the control group, FCM results showed that the cells in G1 phase and the cells in G2 / M phase increased and the apoptosis rate increased in the group of 300nmol / L TSA, the difference was statistically significant (P <0.05). The results of TUNEL assay showed that the apoptosis index increased with the increase of TSA concentration and the prolongation of action time, which was significantly different from the control group (P <0.05). Transmission electron microscopy showed that, after TSA treatment, apoptotic osteosarcoma cells were cytoplasm-concentrated and withered apoptotic bodies. Conclusion: TSA can inhibit proliferation and induce apoptosis of osteosarcoma MNNG / HOS cells in vitro, which may be related to G2 / M cell cycle arrest. HDACI may become a new treatment strategy for osteosarcoma and anti-tumor drugs.