Yang Ji-An, Liu Bao-Hui, Shao Ling-Min, Guo Zhen-Tao, Yang Qian, Wu Li-Quan, Ji Bao-Wei, Zhu Xiao-Nan, Zhang Shen-Qi, Li Cheng-Jun, Chen Qian-Xue
Department of Neurosurgery, Renmin Hospital of Wuhan University Wuhan 430060, Hubei, P. R. China.
Department of Nephrology, Renmin Hospital of Wuhan University Wuhan 430060, Hubei, P. R. China.
Int J Clin Exp Pathol. 2015 Apr 1;8(4):3580-90. eCollection 2015.
The radiotherapy as a local and regional modality is widely applied in treatment of glioma, but most glioblastomas are commonly resistant to irradiation treatment. It remains challengeable to seek out efficient strategies to conquer the resistance of human glioblastoma cells to radiotherapy. Leucine-rich repeats and immunoglobulin-like domains protein 1 (LRIG1) is a newly discovered tumor suppressor which involved in regulation of chemosensitivity in various human cancer cells. In the present study, we established a radioresistant U251 cell line (U251R) to investigate the role of LRIG1 in regulation of radiosensitivity in human glioblastoma cells. Significantly decreased expression level of LRIG1 and enhanced expression of EGFR and phosphorylated Akt were detected in U251R cells compared with the parental U251 cells. U251R cells exhibited an advantage in colony formation ability, which accompanied by remarkably reduced X-ray-induced γ-H2AX foci formation and cell apoptosis. LRIG1 overexpression significantly inhibited the colony formation ability of U251R cells and obviously enhanced X-ray-inducedγ-H2AX foci formation and cell apoptosis. In addition, up-regulated expression of LRIG1 suppressed the expression level of EGFR and phosphorylated Akt protein. Our results demonstrated that LRIG1 expression was related to the radiosensitivity of human glioblastoma cells and may play an important role in the regulation of cellular radiosensitivity of human glioblastoma cells through the EGFR/Akt signaling pathway.
放射治疗作为一种局部和区域治疗方式，广泛应用于胶质瘤的治疗，但大多数胶质母细胞瘤通常对放射治疗具有抗性。寻找有效的策略来克服人类胶质母细胞瘤细胞对放射治疗的抗性仍然具有挑战性。富含亮氨酸重复序列和免疫球蛋白样结构域蛋白1（LRIG1）是一种新发现的肿瘤抑制因子，参与多种人类癌细胞化学敏感性的调节。在本研究中，我们建立了一种耐辐射的U251细胞系（U251R），以研究LRIG1在调节人类胶质母细胞瘤细胞放射敏感性中的作用。与亲本U251细胞相比，在U251R细胞中检测到LRIG1表达水平显著降低，EGFR和磷酸化Akt表达增强。U251R细胞在集落形成能力方面表现出优势，同时伴随着X射线诱导的γ-H2AX灶形成和细胞凋亡显著减少。LRIG1过表达显著抑制U251R细胞的集落形成能力，并明显增强X射线诱导的γ-H2AX灶形成和细胞凋亡。此外，LRIG1表达上调抑制了EGFR和磷酸化Akt蛋白的表达水平。我们的结果表明，LRIG1表达与人类胶质母细胞瘤细胞的放射敏感性相关，可能通过EGFR/Akt信号通路在调节人类胶质母细胞瘤细胞的细胞放射敏感性中发挥重要作用。
