Metadherin contributes to epithelial-mesenchymal transition and paclitaxel resistance induced by acidic extracellular pH in nasopharyngeal carcinoma

Abstract

Paclitaxel resistance is a challenge to the treatment of nasopharyngeal carcinoma (NPC). An acidic extracellular pH (pHe), a hallmark of solid tumors, is demonstrated to decrease the efficacy of chemotherapy. However, the precise function of acidic pHe in mediating chemotherapy in NPC remains unknown. In the present study, acidic pHe significantly decreased the cytotoxicity of paclitaxel in NPC cells. In addition, epithelial-mesenchymal transition (EMT)-like changes were observed in NPC cells cultured at acidic pHe. Metadherin (MTDH), a novel oncogene, is expressed in multiple types of solid tumor, and is associated with several malignant cell characteristics, including malignant cell transformation, proliferation, angiogenesis, chemoresistance, invasion and metastasis. In the present study, MTDH expression was increased in NPC cells that had been cultured at an acidic pHe. Furthermore, the silencing of MTDH expression reversed EMT molecular marker expression and sensitized NPC cells to paclitaxel. Taken together, the results of the present study provide evidence to support an association between acidic pHe-induced paclitaxel resistance and MTDH-mediated EMT in NPC cells. Thus, targeting MTDH may provide a novel strategy for overcoming chemoresistance in NPC therapy.