| 刘静,唐益庭,周俊东,张舒羽,曹晗,吴锦昌,罗居东,陈光烈,曹建平*.蛋白酶体抑制剂MG132联合X射线对人肺腺癌细胞生长迁移和周期的影响及作用机制[J].中华放射医学与防护杂志,2014,34(1):8-12 |
| 蛋白酶体抑制剂MG132联合X射线对人肺腺癌细胞生长迁移和周期的影响及作用机制 |
| Inhibition effect of proteasome inhibitor MG132 combined with X-ray irradiation on cell growth, metastasis and cycle distribution of human lung adenocarcinoma cells |
| 投稿时间：2013-04-26 |
| DOI：10.3760/cma.j.issn.0254-5098.2014.01.003 |
| 中文关键词: 蛋白酶体抑制剂 MG132 肺腺癌 细胞生长 转移 细胞周期阻滞 |
| 英文关键词:Proteasome inhibitor MG132 Lung adenocarcinoma Cell growth Metastasis Cell cycle arrest |
| 基金项目:国家自然科学基金（81372433，81172597，81102078）；江苏省高校重大科研项目（11KJA310001） |
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| 中文摘要: |
| 目的 研究蛋白酶体抑制剂MG132联合X射线对人肺腺癌A549细胞生长、迁移、侵袭、细胞周期分布的影响及机制。方法 MTT法检测不同MG132浓度处理后不同时间肺腺癌A549细胞的增殖；克隆形成实验检测A549细胞的存活能力；划痕实验测定A549细胞的迁移能力；Transwell小室测定其侵袭能力；流式细胞术测定细胞周期分布的改变；Western blot法测定蛋白表达水平。结果 MG132明显抑制人肺腺癌A549细胞的生长，并呈现剂量-效应和时间-效应关系。MG132联合X射线对A549细胞克隆存活能力有显著抑制作用（F=554.78、954.64，P<0.01），且加MG132组克隆存活率均低于照射组（t=4.44、12.41、3.52、6.72，P<0.05）。MG132在无毒性剂量下联合X射线可显著抑制A549细胞的迁移及侵袭能力（t=12.79，P<0.01），并明显增加G1期细胞阻滞（t=4.29，P<0.05）；MG132联合X射线明显降低A549细胞中基质金属蛋白酶-2，-9和G1期相关蛋白Cyclin D1的表达水平，同时增加细胞中P53的表达。结论 MG132可以显著抑制人肺腺癌A549细胞的生长，且在无毒性剂量下联合X射线可以明显降低其转移和侵袭能力，显著增加肿瘤细胞的G1期阻滞。 |
| 英文摘要: |
| Objective To study the effects of proteasome inhibitor MG132 on the growth, metastasis, and cell cycle distribution of human lung adenocarcinoma cells A549 irradiated by X-rays. Methods After treatment of MG132 and irradiation, cell proliferation was detected by MTT assay. Survival was measured by clonogenic assay. Cell migration ability was detected by the Scratch migration assay. Cell invasion ability was detected by transwell migration assay. Cell cycle distribution were analyzed by flow cytometry assay. Protein expression was detected by Western blot assay. Results MG132 alone inhibited cell growth in a dose-and time-dependent manner. MG132 in combination with radiation significantly suppressed the growth, migration and invasion of A549 cells compared to the control(F=554.78, 954.64,P<0.01). MG132 enhanced radiation-induced G1-arrest(t=4.44, 12.41, 3.52, 6.72, P<0.05). The G1 cell cycle distribution rate of MG132 plus RT group was increased to (71.05±4.17)%. The expressions of MMP-2, MMP-9 and Cyclin D1 were significantly suppressed by MG132 in combination with radiation, while the expression of P53 was up-regulated. Conclusions MG132 inhibits cell growth, migration and invasion ability, and induces G1 cell cycle arrest of A549 cells treated with MG132 in combination with radiation, in which the down-regulation of MMPs and Cyclin D1 and up-regulation of P53 may be involved. |
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