Abnormal Wnt signaling and overexpression of ABCG2 contributes to drug efflux properties of side population cells in nasopharyngeal carcinoma

Guan,Guo-Fang; Zhang,De-Jun; Zheng,Ying; Wen,Lian-Ji; Yu,Duo-Jiao; Lu,Yan-Qing; Zhao,Yan

doi:10.3892/mmr.2015.3935

Abnormal Wnt signaling and overexpression of ABCG2 contributes to drug efflux properties of side population cells in nasopharyngeal carcinoma

Authors:
- Guo-Fang Guan
- De-Jun Zhang
- Ying Zheng
- Lian-Ji Wen
- Duo-Jiao Yu
- Yan-Qing Lu
- Yan Zhao
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Affiliations: Department of Otolaryngology, Head and Neck Surgery, The Second Hospital of Jilin University, Changchun, Jilin 130041, P.R. China, Department of Otolaryngology, Head and Neck Surgery, Tumor Hospital of Jilin Province, Changchun, Jilin 130012, P.R. China
Published online on: June 16, 2015 https://doi.org/10.3892/mmr.2015.3935
Pages: 4352-4357

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Abstract

The presence of cancer stem cells (CSCs) has major implications in the choice of cancer treatment strategy and is responsible for tumor relapse. CSCs have been isolated and characterized in several types of cancer; however, studies concerning the CSCs from nasopharyngeal carcinoma (NPC) are limited. Thus, the present study was designed to isolate and characterize the cancer stem-like side population (SP) cells from NPC samples. The fluorescence-activated cell sorting (FACS)-based Hoechst 33342 dye exclusion technique identified that 3.9% of cells from NPC samples were cancer stem-like SP cells. Upon treatment with verapamil (ABC transporter inhibitor), the percentage of SP cells was significantly reduced to 0.7%, which confirms that the ABC transporter protein exhibits a significant role in drug exclusion. Fluorescence microscopy analysis revealed that the FACS purified SP cells showed increased expression of ABCG2 (ATP transporter protein), Oct-4 and CD44 (stem cell surface protein). Furthermore, these SP cells exhibited increased mRNA expression of ABCG2 and anti-apoptotic factor Bmi-1, which contribute to multi-drug resistance and increased cell survival rate. Notably, the Wnt/β-catenin signaling pathways are altered in SP cells. In addition, using reverse transcription‑quantitative polymerase chain reaction analysis it was observed that the cells exhibited increased expression of DKK1 and AXIN2. In conclusion, data from the present study clearly demonstrated that the presence of cancer stem-like SP cells from NPC may be responsible for chemotherapeutic drug resistance, tumor recurrence and invasion.

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