Silencing Op18/stathmin by RNA Interference Promotes the Sensitivity of Nasopharyngeal Carcinoma Cells to Taxol and High-Grade Differentiation of Xenografted Tumours in Nude Mice.

Abstract

Nasopharyngeal carcinoma (NPC) is a refractory tumour, and chemotherapy is one of the primary treatment modalities. Oncoprotein 18 (Op18)/stathmin is a conserved small cytosolic phosphoprotein and highly expressed in tumours, which plays a vital role in maintaining the malignant phenotype of tumours. Taxol is a clinically widely used chemotherapeutic agent for a broad range of taxol-resistant tumours. This study showed that Op18/stathmin silencing by RNA interference (RNAi) combined taxol cooperatively improved cellular apoptosis in CNE1 cells mainly via initiating endogenous death receptor pathway, impaired the capabilities of cellular proliferation and cellular migration and down-regulated the half maximal inhibitory concentration (IC50 ) of taxol, meanwhile decreased the expression of the upstream extracellular regulated kinase 1 (ERK1) in vitro. Evidence also showed that taxol cytotoxicity was markedly augmented for Op18/stathmin RNAi in other NPC cells. In vivo animal experiments have demonstrated that early combination of Op18/stathmin silencing and taxol evidently inhibited tumourigenicity of CNE1 cells and growth of xenografted tumours in nude mice. Remarkably, silencing Op18/stathmin by RNAi still promoted transformation of late-stage CNE1 cells in NPC-xenografted tumours from moderately to highly differentiated and inhibited the pleiotropic cytokine interleukin-10 (IL-10) autocrine by transplanted tumours. These findings suggest that silencing Op18/stathmin by RNAi promotes chemosensitization of NPC to taxol and reverses malignant phenotypes of NPC, which provides a new clue for treating drug-resistant tumours.