【摘要】 目的:研究组蛋白去乙酰化酶抑制剂（HDACi）丁酸钠（NaBt）单独或联合X射线照射对人非小细胞肺癌A549细胞增殖的抑制作用和放射增敏作用,并分析其联合X射线照射对A549细胞周期的影响。方法:对数生长期的A549细胞分为对照组、不同浓度(5、10、15、20和25 mmol·L^-1) NaBt组、4 Gy X射线照射组和不同浓度(5、10、15、20和25 mmol·L^-1) NaBt联合4 Gy X射线照射组,分别在作用后24、48和72h,采用CCK-8法检测各组细胞增殖率。对数生长期的A549细胞分为对照组、10 mmo)l·L^-1NaBt组、20 mmo)l·L^-1 NaBt组、4 Gy X射线照射组、10 mmol·L^-1NaBt联合4 Gy X射线照射组和20 mmol·L-¹ NaBt联合4 Gy X射线照射组,作用后24 h,采用流式细胞术检测各组不同细胞周期A549细胞百分率。结果:与对照组比较,作用48 h后5、10、15、20和25 mmol·L^-1NaBt组细胞增殖率均明显降低（P<0.05或P<0.01）,作用72h后5、10、15、20和25 mmol·L^-1NaBt组细胞增殖率明显降低（P<O.0l）,并呈浓度和时间依赖性。作用48 h后,分别与对照组、4 Gy X射线照射组及相对应浓度NaBt组比较,15、20和25 mmol·L-1NaBt联合4 Gy X射线照射组细胞增殖率均明显降低（P<0.05或P<0.01）;作用72 h后,分别与对照组和4 Gy X射线照射组比较,不同浓度NaBt联合4 Gy X射线照射组细胞增殖率明显降低（P<0.01）,且20和25 mmol·L^-1NaBt联合4 Gy X射线照射组细胞增殖率明显低于相对应浓度NaBt组（P<0.01）。细胞周期检测,作用24 h后,与对照组比较,10和20 mmol·L^-1NaBt组G₀/G₁期和G₂+M期细胞百分率明显升高（P<0.05或P<0.01）,S期细胞百分率明显降低（P<0.01）;4 Gy X射线照射组和10 mmol·L^-1 NaBt联合4 Gy X射线照射组G₂+M期细胞百分率明显升高（P<0.01）,G₀/G₁期和S期细胞百分率明显降低（P<0.01）。结论:NaBt对A549细胞具有增殖抑制作用和放射增敏作用,并呈浓度和时间依赖性,且NaBt和X射线的联合抑制效果明显优于二者单独应用,其机制可能与二者联合引起A549细胞G₂+M期阻滞有关。更多还原

【Abstract】 Objective:To study the inhibitory effect and radiosensitization effects of sodium butyrate(NaBt),a histone deacetylase inhibitor(HDACi),on the proliferation of human non-small cell lung cancer A549 cells alone or in combination with X-ray irradiation,and to analyze its combined effect with irradiation on the cell cycle of A549 cells. Methods:The A549 cells in logarithmic growth phase were divided into control group,different concentrations(5,10,15,20,and 25 mmol·L-1)of NaBt groups,4 Gy X-ray irradiation group and different concentrations(5,10,15,20,and 25 mmol·L-1)NaBt combined with 4 Gy X-ray irradiation groups. CCK-8 method was used to detect the cell proliferation rates in various groups at24,48 and 72 h after treatment. The changes of cell cycle were analyzed by flow cytometry. The A549 cells in logarithmic growth phase were divided into control group, 10 mmol·L-1 NaBt group,20 mmol·L-1 NaBt group,4 Gy X-ray irradiation group,10 mmol·L-1 NaBt combined with 4 Gy X-ray irradiation group,and 20 mmol ·L-1 NaBt combined with 4 Gy X-ray irradiation group. At 24 h after treatment,the percentages of A549 cells in each phase of cell cycle in various groups were analyzed.Results:After 48 h of treatment,the cell proliferation rates in 5,10,15,20,and 25 mmol·L-1 NaBt groups were significantly lower than that in control group(P<0. 05 or P<0. 01);after 72 h of treatment,the cell proliferation rates in 5,10,20,and 25 mmol·L-1 NaBt groups were significantly lower than that in control group(P<0. 01) in a concentration-and time-dependent manner;after treated for 48 h,the cell proliferation rates in 15,20,and 25 mmol·L-1 NaBt combined with 4 Gy X-ray irradiation groups were significantly lower than those in control group,4 Gy X-ray irradiation group and corresponding concentrations of NaBt groups(P<0. 05 or P<0. 01);after treated for 72 h,compared with control group and 4 Gy X-ray irradiation group,the cell proliferation rates in different concentrations of NaBt combined with 4 Gy X-ray irradiation groups were significantly decreased(P<0. 01);the cell proliferation rates in 20 and 25 mmol·L-1 NaBt combined with 4 Gy X-ray irradiation groups were significantly lower than those in corresponding concentrations of NaBt groups(P<0. 01). The cell cycle analysis results showed that after 24 h of treatment,compared with control group,the percentages of A549 cells in G0/G1 phase and G2+ M phase in 10 and 20 mmol·L-1 NaBt groups were significantly increased(P<0. 05 or P<0. 01),and the percentage of A459 cells in S phase was significantly decreased(P<0. 01);the percentages of cells in G2+M phase in 4 Gy X-ray irradiation group and 10 mmol·L-1 NaBt combined with 4 Gy X-ray irradiation group were significantly increased(P<0. 05 or P<0. 01),and the percentages of cells in G0/G1 phase and S phase were significantly decreased(P<0. 01). Conclusion:NaBt has the inhibitory effect on the proliferation of A549 cells and radiosensitization effect in a concentration-and time-dependent manner,and the combined inhibitory effect of NaBt and X-ray is better than both of them used alone;its mechanism may be related to G2+ M phase arrest of the A549 cells induced by combination of NaBt and X-ray.更多还原