MG-132 reverses multidrug resistance by activating the JNK signaling pathway in FaDu/T cells

Abstract

Multidrug resistance (MDR) is a major impediment to cancer therapy. MG-132 has been identified to be effective against MDR in several types of cancer. However, the mechanism of MG-132 in head and neck squamous cell carcinomas remains unknown. Based on our previous study, the present detected P-gp and P-gp expression in hypopharyngeal carcinoma FaDu cells, revealing that their expression was lower than that observed in the MDR cell line FaDu/T. To reverse the MDR of FaDu/T cells, the present study introduced MG-132 and demonstrated that the high expression of P-gp/P-gp in FaDu/T cells was attenuated in a time-dependent manner. MG-132 also strengthened the sensitivity of FaDu/T cells to multidrugs. c-Jun N-terminal kinase (JNK) activation was further observed in FaDu/T cells. However, P-gp/P-gp did not decrease when FaDu/T cells were pretreated with SP600125. These results indicated that MG-132 reversed the MDR of hypopharyngeal carcinoma by downregulating P-gp/P-gp, and the underlying mechanism may be associated with the activation the of the JNK signaling pathway.