MG132 enhances the radiosensitivity of lung cancer cells in vitro and in vivo
MG132 enhances the radiosensitivity of lung cancer cells in vitro and in vivo
复制标题
MG132增强肺癌细胞体内外放射敏感性
DOI：
10.3892/or.2015.4169
复制
发表时间：
2015-10-01
期刊：
影响因子：
4.2
通讯作者：
Cao, Jianping
中科院分区：
文献类型：
--
作者：
Zhu, Wei;Liu, Jing;Cao, Jianping
放射治疗是肺癌常用的治疗手段，然而放射抵抗仍然是取得最大疗效的根本障碍。癌细胞利用泛素-蛋白酶体系统(UPS)促进增殖和减少细胞凋亡。MG132(Cbboxyl-Leucinyl-H)是一种特异性和选择性的26S蛋白酶体可逆抑制物，已在多种癌症中显示出抗癌作用。此前，我们曾报道过MG132增强辐射对肺癌细胞的抗生长和抗转移作用。然而，MG132能否在体内外增强肺癌细胞的放射敏感性仍是个未知数。在本研究中，我们发现MG132增加了辐射处理的A549和H1299细胞的凋亡率和双着丝粒染色体比例。MG132 plus细胞辐射诱导的核因子-kappa B表达和I-kappa Bα磷酸化均减弱。H1299裸鼠移植瘤的体内模型显示，MG132加照射组移植瘤体积小于单纯照射组、MG132组和对照组。此外，MG132加照射组Ki67的表达明显降低。综上所述，这些结果表明MG132在体内外通过多种机制增强放射敏感性。
Radiotherapy is a common treatment modality for lung cancer, however, radioresistance remains a fundamental barrier to attaining the maximal efficacy. Cancer cells take advantage of the ubiquitin-proteasome system (UPS) for increased proliferation and decreased apoptotic cell death. MG132 (carbobenzoxyl-leucinyl-leucinyl-leucinal-H), a specific and selective reversible inhibitor of the 26S proteasome, has shown anticancer effect in multiple types of cancers. Previously, we have reported that MG132 enhances the anti-growth and anti-metastatic effects of irradiation in lung cancer cells. However, whether MG132 can enhance the radiosensitivity in lung cancer cells in vitro and in vivo is still unknown. In this study, we found that MG132 increased apoptosis and dicentric chromosome ratio of A549 and H1299 cells treated by irradiation. Radiation-induced NF-kappa B expression and I kappa B alpha phosphorylation was attenuated in MG132 plus irradiation-treated cells. The in vivo model of H1299 xenografts of nude mice showed that the tumor size of MG132 plus irradiation treated xenografts was smaller than that of irradiation, MG132 or the control group. Moreover, MG132 plus irradiation group showed significant reduced Ki67 expression. Taken together, these results demonstrate that MG132 enhances the radiosensitivity through multiple mechanisms in vitro and in vivo.