目前国际上局限期小细胞肺癌（SCLC）治疗指南均推荐化疗开始后应尽早放疗，但数据来源于临床，无基础实验支持。我们前期发现化疗耐药型SCLC患者和两株耐药细胞株中，N乙酰氨基葡萄糖转移酶Ⅴ(GnT-Ⅴ)的表达和放射抵抗性明显提高。下调耐药细胞中GnT-Ⅴ表达可降低其放射抵抗性。所以我们提出GnT-Ⅴ可能参与SCLC化疗诱导的耐药对放射抵抗性的影响。为进一步探讨该机制，并分析GnT-Ⅴ参与放射抵抗性调控的分子网络，本项目拟开展以下研究①化疗药重新诱导SCLC细胞，从体内外观察在诱导耐药过程中GnT-Ⅴ和放射抵抗性的改变。②利用临床标本分析GnT-Ⅴ与SCLC患者耐药、放射抵抗性和预后的关系。③基因芯片和蛋白质组学技术探讨GnT-Ⅴ参与放射抵抗性调控的分子网络。本项目将为局限期SCLC化疗开始后应尽早放疗提供基础实验数据，期望能基于GnT-Ⅴ降低化疗诱导耐药对放射抵抗性的影响，提高患者临床疗效。

All the international cancer guidelines suggest that the radiation therapy should be performed as soon as possible after the beginning of chemotherapy for limited-stage small cell lung cancer(SCLC). However, the guides were made according to the clinical trials, without experimental data to support. Our previous studies revealed that the radiation resistance and expression of N-Acetylglucosaminyltransferases-Ⅴ(GnT-Ⅴ) were both significantly higher in SCLC patients with chemoresistance than those in chemotherapy sensitivity patients.This phenomenon was also found in the two SCLC drug resistance cells H69AR and H446AR. Besides, the radiation resistance was decreased by down-regulation of GnT-Ⅴin drug resistance cells. So, the mechanism that GnT-Ⅴ might be involved in the radiation resistance caused by chemotherapy induced drug resistance was proposed. To further study this mechanism and further analyze the network of GnT-Ⅴcontrolling radiation resistance,the following studies will be done: firstly,the changes of GnT-Ⅴexpression and radiation resistance were measured in vivo and in votro in the process of inducing drug resistance cells again; secondly, the role of GnT-Ⅴ in drug resistance, radiation resistance and prognosis of SCLC patients was explored by clinical samples;the last one, the network of GnT-Ⅴ controlling cell radiation resistance was studied by cDNA microarray and proteomic technique. The studies will provide experimental data to support the important role of early radiation therapy in limited-stage SCLC, and the way to decrease radiation resistance caused by chemotherapy induced drug resistance to improve the prognosis of SCLC patients based on GnT-Ⅴ pathway.