Potential benefits of combined treatment with Hsp90 inhibitor AUY922 and cisplatin for overcoming drug resistance in nasopharyngeal carcinoma.

Abstract

Nasopharyngeal carcinoma (NPC) initially responds well to platinum-based therapy but often develops resistance. Combining therapies may offer a viable approach to address this resistance. Heat shock protein 90 (Hsp90) has shown promising anticancer activity in various cancer types. This study aimed to investigate the efficacy of an Hsp90 inhibitor, luminespib (AUY922), and evaluate the synergistic effect of combining AUY922 with cisplatin on two cisplatin-resistant human NPC cell lines. The response of cisplatin-resistant NPC cells to AUY922 and/or cisplatin was assessed through proliferation assay, cell cycle analysis, Annexin V apoptosis detection, Western blot analysis, in vivo investigation, and histological analysis. Our results indicated that AUY922/cisplatin combination significantly inhibited the proliferation of both non-resistant and resistant NPC cells. Moreover, Annexin V analysis indicated apoptosis when AUY922 was administered alone or in combination with cisplatin. Consistently, Western blot analysis revealed increased cleavage of PARP. Most importantly, the combination treatment demonstrated enhanced tumor growth inhibition in nude mice xenograft models, without notable adverse effects. These findings highlight the antiproliferative effects and anticancer activity of the AUY922/cisplatin combination in cisplatin-resistant NPC cells. The combination treatment of AUY922 and cisplatin holds promise as a strategy to overcome drug resistance in NPC patients.