NK/T细胞淋巴瘤（NKTL）侵袭性强，对化疗耐药，患者预后差。研究表明NKTL高表达白介素-2受体α (IL-2Rα)，且与预后密切相关，推测IL-2Rα在NKTL的发生发展及化疗耐药中起到重要作用。本研究采用LMP-1/pcDNA3.1质粒转染的NK-92及KHYG-1细胞系，联合NF-κB抑制剂来检测IL-2Rα的表达情况，探讨IL-2Rα的表达机制及其与EB病毒的关系；然后采用IL-2Rα/pcDNA3.1质粒转染的SNK-6及NK-92细胞系，通过克隆形成实验、细胞周期分析、周期相关蛋白检测，探讨IL-2Rα促细胞增殖的机制；MTT实验检测上述细胞系对常见化疗药物的敏感性，通过检测凋亡及抗凋亡相关蛋白的表达、多药耐药相关基因的表达及mTOR通路、自噬系统的活化情况，探讨IL-2Rα介导化疗耐药的机制，并应用IL-2Rα抗体抑制上述作用机制，探讨IL-2Rα靶向治疗的潜在应用价值。

Natural killer/T cell lymphoma is highly aggressive, featured by resistance to common chemotherapy drugs, and the prognosis is very poor. High level of interleukin-2 receptor α (IL-2Rα) expression was demonstrated in NKTL patients, and the level of IL-2Rα was significantly related to the treatment responses and prognosis, which suggested that IL-2Rα may be involved in the pathogenesis of NKTL and contributed to the chemoresistance of NKTL. In this study, NKTL cell lines (SNK-6, SNT-8, NK-92, KHYG-1) and LMP-1/pcDNA3.1-transfected cell lines (NK-92, KHYG-1) will be used to detect the role of LMP-1 and NF-κB in the expression mechanism of IL-2Rα in Epstein-Barr virus positive NKTL. Then, using SNK-6, NK-92, IL-2Rα/pcDNA3.1-transfected SNK-6 and NK-92 cell lines, we will investigate the mechanism of proliferation induced by IL-2Rα through soft agar colony formation assay, cell cycle analysis, and detection of cell cycle related proteins. Furthermore, these cell lines will be used to determine the resistance ability to common chemotherapy drugs such as doxorubicin, gemcitabine, oxaliplatin, and asparaginase, and we will investigate the chemoresistance mechanisms mediated by IL-2Rα through detection of apoptosis and anti-apoptosis related proteins, multidrug resistance related genes and proteins, asparagine synthetase, glutamine synthetase, status of mTOR pathway and autophagy system. Finally, anti-IL-2Rα antibody will be used to inhibit the mechanisms mentioned above, and we will explore the potential role of targeted therapy against IL-2Rα.