MG132联合X射线对非小细胞肺癌生长转移和凋亡的影响

Effects of proteasome inhibition on growth,metastasis,and apoptosis of non-small cell lung cancer induced by X-rays irradiation

探讨蛋白酶体抑制剂MG132联合X射线对非小细胞肺癌H1299细胞生长、转移侵袭和细胞凋亡的影响及机制。采用MTT法检测不同MG132浓度不同时间处理后肺癌H1299细胞的增殖;Transwell小室实验测定肺癌细胞的迁移和侵袭能力;流式细胞术测定肺癌细胞的凋亡;Western-blot法测定蛋白表达水平。结果表明,MG132能明显抑制H1299细胞的生长,并呈现剂量-效应和处理时间-效应关系;MG132在无毒性剂量下联合X射线可显著抑制H1299细胞的迁移及侵袭能力,并明显诱导细胞凋亡;MG132能明显降低H1299细胞的基质金属蛋白酶-2、-9的表达水平,降低抗凋亡蛋白Bcl-2的表达水平,同时增加凋亡蛋白Bax的表达水平。提示MG132可以显著抑制人非小细胞肺癌H1299细胞的生长,且在无毒性剂量下联合X射线可以明显降低癌细胞转移和侵袭能力,能显著加强X射线诱导的细胞凋亡作用。

After H1299 cells were treated with MG132, the cellular proliferation was detected by MTT assay; Transwell migration assay was used to determine the migration and invasion ability of H1299 cells in vitro.; changes of cell apoptosis were analyzed by flow cytometry assay; Western blot assay was employed to measure the protein expression. The results show that MG132 alone inhibits cell growth in H1299 cells, in a dose- and time-dependent manner; MG132 in combination with radiation significantly suppresses the migration and invasion of H1299 cells; MG132 enhances radiation-induced apoptosis in H1299 cells. The apoptosis rate of MG132＋RT group is up to （11.44±0.90）%; the expression of MMP-2, -9, Bcl-2 is significantly suppressed by MG 132 in combination with radiation, while the expression of Bax is up-regulated relatively. The present findings demonstrate that MG132 inhibits the cell growth in lung cancer, the migration and invasion ability of H1299 cells treated by MG132 in combination with radiation is significantly suppressed, while the apoptosis rate increases relatively. The mechanism may be associated with MMPs and Bcl-2 down-regulation, as well as Bax up-regulation.