| 祁丽 张文轩 邢帆 陈敏 何欣阳 邢丽娜.组蛋白去乙酰化酶抑制剂SAHA对胰腺癌细胞Patu8988 的放射增敏作用[J].,2016,16(33):6583-6586 |
| 组蛋白去乙酰化酶抑制剂SAHA对胰腺癌细胞Patu8988 的放射增敏作用 |
| Radiosensitizing Effect of SAHA on the Pancreatic Cancer Patu8988 Cells |
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| DOI： |
| 中文关键词: 组蛋白去乙酰化酶 胰腺癌 SAHA 放射增敏 增殖 |
| 英文关键词: Histone deacetylase HDAC Pancreatic cancer SAHA Radiosensitization Proliferation |
| 基金项目:黑龙江省卫生厅科研基金项目(2013059) |
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| 中文摘要: |
| 目的：探讨组蛋白去乙酰化酶抑制剂SAHA对胰腺癌Patu8988 细胞增殖的影响和放射增敏作用。方法：用含不同浓度(0、
0.5、1、2、4、6、8 umoL/L)SAHA 的培养基分别培养胰腺癌Patu8988细胞12、24、36 和48 h，采用MTT 比色法检测SAHA作用细
胞的生长抑制作用，计算IC50。设空白对照组和SAHA 处理组(20%IC50 SAHA作用24 h)，予6MV-X射线(0、2、4、6、8Gy)照射，
克隆形成实验法检测SAHA对Patu8988 细胞的放射增敏作用，单靶多击模型拟合细胞存活曲线，计算放射相关参数D0、Dq 值和
放射增敏比。Western blot 法检测不同浓度(0、4、8、12 滋moL/L)SAHA 对Patu8988细胞内组蛋白H4 乙酰化水平、Ku70 和Bax 蛋
白表达的影响。结果：SAHA可抑制Patu8988 细胞增殖，呈浓度和时间依赖性，48 h的IC50为5.40 umol/L。SAHA 联合放疗处理
Patu8988 细胞的克隆形成率明显低于单独放疗处理，D0 分别为1.513、2.229，Dq 分别为0.783、1.321，放射增敏比(SER)为1.47。
SAHA可增加Patu8988 细胞内组蛋白H4 乙酰化水平，抑制DNA 修复蛋白Ku70 表达，促进凋亡相关基因Bax表达，呈剂量依赖
性，差异有统计学意义(P<0.05)。结论：SAHA可以浓度和时间依赖性方式抑制胰腺癌Patu8988 细胞的增殖，并具有放射增敏作
用，抑制断裂DNA 双链修复及促进凋亡可能是其作用机制之一。 |
| 英文摘要: |
| Objective:To investigate the effect of SAHA on the radiosensitization and proliferation of pancreatic cancer cell line
Patu8988.Methods:Different concentrations (0, 0.5, 1, 2, 4, 6, 8 umoL/L) of SAHA were treated in human pancreatic cancer cell line
Patu8988 for 12, 24, 36 and 48 h, the growth inhibition was detected by MTT colorimetric assay, and the effect of IC50 was calculated.
The blank control group and SAHA treatment group (20%IC50 SAHA 24 h) were set and treated by 6MV-X (0, 2, 4, 6, 8Gy) irradiation,
clone formation radiosensitizing effect on Patu8988 cells was examined by SAHA assay, multi-target click model fitting cell survival
curve, radiation related parameters of D0, Dq the value and radiosensitization ratio were calculated. Western Blot was used to detect the
effects of different concentrations (0, 4, 8, 12 umoL/L) of SAHA on the level of histone H4 acetylation, Ku70 and Bax protein expression
in Patu8988 cells.Results:SAHA could inhibit the proliferation of Patu8988 cells in a concentration and time dependent, the IC50 of 48h
was 5.40 滋mol/L. The colony formation rate of SAHA cells treated with Patu8988 combined with radiotherapy was significantly lower
than that of radiotherapy alone. The D0 was 1.513, 2.229, Dq were 0.783 and 1.321, respectively, and the radiation enhancement ratio
(SER) was 1.47. SAHA could increase the level of histone H4 acetylation in Patu8988 cells, inhibit the expression of DNA repair protein
Ku70, and promote the expression of apoptosis related genes Bax in a dose-dependent manner (P<0.05).Conclusion:SAHA could inhibit
the proliferation of pancreatic cancer Patu8988 cells in a concentration and time-dependent manner and had radiosensitizing effect, it
might be related to the inhibition of DNA double strand repair and promotion of apoptosis. |
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