Objectives

 Methods Tumor initiating capability of HNC-CH133+ cells with ZEB1/2 knockdown or co-overexpression was presented in vitro and in vivo.

 Results In the present study, we demonstrated that ZEB1/ZEB2 expression was significantly increased in HNC-CD133+ CSC-like cells compared with HNC-CD133− cells. The small interfering RNA (siRNA)-mediated co-knockdown of ZEB1 and ZEB2 (siZEB1/2) in HNC-CH133+ cells suppressed their CSC-like properties, including self-renewal ability, the expression of stemness markers, and drug resistance. In contrast, the co-overexpression of ZEB1/ZEB2 in HNC-CD133− cells enhanced their sphere-forming ability and increased the percentage of CD44-positive cells and side population cells. In vivo studies showed that the delivery of siZEB1/2 to xenograft tumors in nude mice reduced tumor growth and the rate of distant metastasis. In clinical samples, the levels of ZEB1/ZEB2 expression were low in local lesions but high in metastatic lymph nodes in HNC tissues. Patients with tumors that co-expressed ZEB1high and ZEB2high had especially poor survival rates.

 Conclusion Therapies targeting ZEB1/ZEB2 in HNC-CD133+ cells may provide a new approach for HNC therapy in the future.

 Source: Journal of Oral Oncology

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