Department of Otolaryngology, Xiangya Hospital, Central South University, Changsha 410008, PR China.
Oncol Rep. 2012 Apr;27(4):987-94. doi: 10.3892/or.2011.1586. Epub 2011 Dec 8.
Radioresistance continues to be a major problem in the treatment of nasopharyngeal carcinoma (NPC). This study aimed to identify novel proteins associated with NPC radio-resistance. We used a mass spectrometry driven-proteomic strategy to identify novel proteins associated with NPC radio-resistance, and differential proteins were subsequently processed by bio-informatic analysis. As a result, twelve proteins were identified with aberrant expression in radioresistant (RR) NPC tissues compare to radiosensitive (RS) NPC tissues. Among these proteins, ERp29, Mn-SOD, HSP27 and GST ω1 were found to be significantly up-regulated in RR NPC tissues, and ERp29 was selected for further validation. Immunohistochemistry analysis confirmed that ERp29 was overexpressed in RR NPC tissues compared with RS NPC tissues. To prove the role of ERp29 in the induction of NPC radioresistance, ERp29 was down-regulated in the ERp29 enriched NPC cells CNE-1 and 6-10B by specific shRNA. Radiosensitivity was measured using cell proliferation assay and clonogenic survival assay, and cell apoptosis was measured using flow cytometric analysis. We found that ERp29 knockdown attenuated CNE-1 and 6-10B cell radioresistance and enhanced cell apoptosis. These results suggest that ERp29 associates with radioresistance in NPC, and ERp29 could be a potential biomarker for predicting NPC response to radiotherapy.
放射抗拒性仍是鼻咽癌(NPC)治疗中的一个主要问题。本研究旨在鉴定与 NPC 放射抗拒性相关的新蛋白。我们使用基于质谱的蛋白质组学策略来鉴定与 NPC 放射抗拒性相关的新蛋白,随后对差异蛋白进行生物信息学分析。结果,在放射抗拒性(RR)NPC 组织与放射敏感性(RS)NPC 组织相比,鉴定出 12 种表达异常的蛋白。在这些蛋白中,RR NPC 组织中 ERp29、Mn-SOD、HSP27 和 GSTω1 明显上调,其中 ERp29 被选择进行进一步验证。免疫组织化学分析证实 RR NPC 组织中 ERp29 的表达高于 RS NPC 组织。为了证明 ERp29 在诱导 NPC 放射抗拒性中的作用,我们通过特异性 shRNA 下调了富含 ERp29 的 NPC 细胞 CNE-1 和 6-10B 中的 ERp29。通过细胞增殖试验和集落形成生存试验测量放射敏感性,并通过流式细胞术分析测量细胞凋亡。我们发现 ERp29 敲低可减弱 CNE-1 和 6-10B 细胞的放射抗拒性并增强细胞凋亡。这些结果表明 ERp29 与 NPC 中的放射抗拒性相关,ERp29 可能是预测 NPC 对放射治疗反应的潜在生物标志物。