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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
Author(s) -
Lin Xuechi,
Yu Ting,
Zhang Lingxi,
Chen Sangyan,
Chen Xian,
Liao Ying,
Long Dan,
Shen Fang
Publication year - 2016
Publication title -
basic and clinical pharmacology and toxicology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.805
H-Index - 90
eISSN - 1742-7843
pISSN - 1742-7835
DOI - 10.1111/bcpt.12633
Subject(s) - stathmin , gene silencing , cancer research , rna interference , nasopharyngeal carcinoma , biology , nude mouse , apoptosis , microbiology and biotechnology , medicine , rna , phosphorylation , radiation therapy , biochemistry , gene
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 ( RNA i) combined taxol cooperatively improved cellular apoptosis in CNE 1 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 ( IC 50 ) of taxol, meanwhile decreased the expression of the upstream extracellular regulated kinase 1 ( ERK 1) in vitro . Evidence also showed that taxol cytotoxicity was markedly augmented for Op18/stathmin RNA i in other NPC cells. In vivo animal experiments have demonstrated that early combination of Op18/stathmin silencing and taxol evidently inhibited tumourigenicity of CNE 1 cells and growth of xenografted tumours in nude mice. Remarkably, silencing Op18/stathmin by RNA i still promoted transformation of late‐stage CNE 1 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 RNA i promotes chemosensitization of NPC to taxol and reverses malignant phenotypes of NPC , which provides a new clue for treating drug‐resistant tumours.