ABCG2与消化系统肿瘤相关研究进展

The progress of ABCG2 in tumor of digestive system

临床实践中,很多肿瘤因具有了多药耐药性(MDR)而对抗肿瘤药治疗无效,其中一重要的机制是与多药耐药转运蛋白相关。ABCG2是ABC转运超家族的一个成员,可转运包括拓扑替康、伊立替康等细胞毒药物,但ABCG2具体的蛋白结构及如何转运这些结构不同的底物的机制尚不明确。本文综述近期ABCG2基础研究成果及与消化系统肿瘤相关研究的进展。这些研究提示ABCG2在食管癌、胃癌、肠癌中肿瘤细胞产生多药耐药机制发挥了重要作用,并可能与预后相关。同时ABCG2基因的单核苷酸多态性(SNP)影响ABCG2蛋白的表达、分布和功能,从而可能导致肿瘤对相关药物的耐药性及作为提示预后差的指标。

Many tumors fail to respond to chemotherapy by acquiring MDR（ multiple drug resistance）in clinic. The phenotype of MDR has been correlated with the presence of MDR transporters that actively transport drugs out of the cell. ABCG2 is a member of the ATP binding cassette （ABC） superfamily, and it function is as a pump to translocate several eytotoxic drugs, including topotecan and irinotecan. However, the high-resolution structure of ABCG2 and its in- teraction with a variety of substrates are still unclear. Here, we reviewed recent studies on ABCG2 expression pattern, structure, function and its relation to gastrointestinal cancers. Several studies have indicated that ABCG2 might play a critical role of MDR in esophageal cancer, stomach cancer and colon cancer and negatively affect patient prognosis. Meanwhile, the single nucleotide polymorphisms（SNPs）of ABCG2 gene have been suggested to influence ABCG2 ex- pression, location and transport activity. These changes might be associated with MDR in cancer cells and serve as a poor prognostic marker.