GPxs对非小细胞肺癌铂类化疗药物耐药影响的研究

项目名称： GPxs对非小细胞肺癌铂类化疗药物耐药影响的研究

项目编号： No.81201732

项目类型： 青年科学基金项目

立项/批准年度： 2013

项目学科： 肿瘤学1

项目作者： 陈柏深

作者单位： 南方医科大学

项目金额： 23万元

中文摘要： 肺癌对铂类化疗药物的高耐药性严重制约肺癌临床治疗的发展，但其机制目前尚不清楚。本研究项目前期研究已证实GPxs抗过氧化物酶家族在恶性肿瘤中存在表达差异并受甲基化修饰调节。其家族成员GPx3编码基因甲基化能准确预测头颈部癌患者对铂类化疗药物耐药趋势和预后，而另一家族成员GPx1则功能上介导头颈部癌对铂类耐药。相反，GPx3高表达与非小细胞肺癌对铂类化疗药物耐药呈正相关。但GPxs家族在非小细胞肺癌表观遗传学调节方式和介导非小细胞肺癌对铂类化疗药物耐药的机制和信号通道尚不清楚。本项目拟通过临床标本、细胞株两个层面，结合甲基化检测、基因干扰、裸鼠成瘤实验等手段进一步明确整个GPxs家族在非小细胞肺癌表达规律和其编码基因甲基化情况，其与临床患者铂类化疗药物耐药的关系，以及介导非小细胞肺癌耐药的具体分子机制，为探索临床预测非小细胞肺癌铂类耐药的生物标志物和逆转铂类耐药性打下基础。

中文关键词： 非小细胞肺癌；顺铂耐药性；谷胱甘肽过氧化物酶1；活性氧化物；AKT信号通道

英文摘要： High incidence of platin chemoresistance has seriously limited the progression of chemotherapy in lung cancer,and the mechanism underlying is still unclear.We had verified that their was difference in the exppression of coding genes of GPxs family due to methylation modification in cacinomas. GPx3,one member of GPxs family,is a outstanding biological marker for predicting platin chemoresistance and prognosis of HNC precisely.Meanwhile,GPx1,another member of GPxs family,funtioanlly induce platin chemoresistance .Oppositely, We further found that over expression of GPx3 positively related to paltin chemoresistance. However,the way of epigenetic regulation of GPxs family and the mechanism of signal pathway mediating platin chemoresistance is still unclear in NSCLC.Therefore,we plan to conduct this study to determine the rule of the expression and epigenetic regulation of the whole GPxs family,the relationship between the expression and methylation of coding gene of GPxs and paltin chemoresistance as well as specific molecular mechanism mediating platin chemoresistance in NSCLC via applying different biologiacal tethnologies including methylation detection,gene interference and nude mouse tumorigenesis on clinic samples and cell lines,to explore the biomaker for predicting platin resistance and the way for restoring

英文关键词： non small cell lung cancer；resistance to cisplatin；GPx1；ROS；AKT signal pathway