p38 MAPK通路介导的EMT在人胃癌细胞多药耐药中的作用与机制研究

It has been showed that epithelial-mesenchymal transition (EMT) was not only one of the core mechanism of tumor cell metastasis, but also it’s one of the major mechanisms of tumor cells resistant to chemotherapy. the mesenchymal-like cells in tumor are more resistant to chemotherapeutic drugs than those of epithelial-like cells. It is also well-accepted that p38 MAPK pathway plays as a key regulator in EMT. Our update research data shows that chemotherapeutic drugs induce activation of p38 MAPK pathway, promote EMT in gastric cancer cells. Therefore, we hypothesize that in gastric cancer cells, chemotherapeutic drugs activate the p38 MAPK signal and promote EMT through upregulation of p38 phosphorylation; the activated p38 MAPK then improve the expression and activity of ATP-binding cassette (ABC) transporter protein through increased expression of EMT associated transcriptional factors, and finally cause the multi-drug resistance and metastasis. This study will clarify the above hypothesis by means of in vitro and in vivo. The work will be very helpful to look for theoretical basis on reversing multi-drug resistance of gastric cancer cells.

最新研究显示上皮细胞间叶样表型转化（EMT）不仅是肿瘤细胞转移的核心机制之一，也是肿瘤细胞产生化疗耐药性的主要机制之一，间叶样细胞较之上皮样细胞有更强的化疗抵抗能力。有研究表明，在EMT过程中，p38 MAPK信号通路起着重要的调节作用。申请人前期研究发现化疗药物诱导p38 MAPK通路激活，促使胃癌细胞发生EMT。据此，我们推测化疗药物可能通过激活p38 MAPK信号通路，上调其下游靶蛋白－EMT 相关转录因子的表达和活性、增加三磷酸腺苷结合盒（ATP-binding cassette, ABC）转运蛋白的表达，使胃癌细胞发生 EMT、产生多药耐药性并易于转移。本研究拟应用分子和细胞生物学技术在细胞和动物模型中对上述推论加以证实。如能证实上述推论将非常有助于进一步阐明胃癌细胞化疗耐药机制，为克服化疗耐药提供理论依据。

最新研究显示上皮细胞间叶样表型转化（EMT）不仅是肿瘤细胞转移的核心机制之一，也是肿瘤细胞产生化疗耐药性的主要机制之一，间叶样细胞较之上皮样细胞有更强的化疗抵抗能力。有研究表明，在EMT过程中，p38 MAPK信号通路起着重要的调节作用。申请人前期研究发现化疗药物诱导p38 MAPK通路激活，促使胃癌细胞发生EMT。据此，我们推测化疗药物可能通过激活p38 MAPK信号通路，上调其下游靶蛋白－EMT 相关转录因子的表达和活性、增加三磷酸腺苷结合盒（ATP-binding cassette, ABC）转运蛋白的表达，使胃癌细胞发生 EMT、产生多药耐药性并易于转移。本研究拟应用分子和细胞生物学技术在细胞和动物模型中对上述推论加以证实。本研究按照基本证实如上假说，体内实验正在进行。上述结论将非常有助于进一步阐明胃癌细胞化疗耐药机制，为克服化疗耐药提供理论依据。