STAT3 blockade enhances the efficacy of conventional chemotherapeutic agents by eradicating head neck stemloid cancer cell

Lin-Lin Bu; Zhi-Li Zhao; Jian-Feng Liu; Si-Rui Ma; Cong-Fa Huang; Bing Liu; Wen-Feng Zhang; Zhi-Jun Sun

doi:10.18632/oncotarget.5986

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Research Papers:

STAT3 blockade enhances the efficacy of conventional chemotherapeutic agents by eradicating head neck stemloid cancer cell

Lin-Lin Bu, Zhi-Li Zhao, Jian-Feng Liu, Si-Rui Ma, Cong-Fa Huang, Bing Liu, Wen-Feng Zhang and Zhi-Jun Sun _

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Oncotarget. 2015; 6:41944-41958. https://doi.org/10.18632/oncotarget.5986

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Abstract

Lin-Lin Bu1,2, Zhi-Li Zhao1, Jian-Feng Liu1, Si-Rui Ma1, Cong-Fa Huang1, Bing Liu1,2, Wen-Feng Zhang1,2, Zhi-Jun Sun1,2

1The State Key Laboratory Breeding Base of Basic Science of Stomatology & Key Laboratory of Oral Biomedicine Ministry of Education, Wuhan, China

2Department of Oral Maxillofacial-Head Neck Oncology, School and Hospital of Stomatology, Wuhan University, Wuhan, China

Correspondence to:

Zhi-Jun Sun, e-mail: [email protected]

Keywords: STAT3, head neck squamous cell carcinoma, cancer stem cell, S3I-201, chemotherapy

Received: June 20, 2015 Accepted: October 01, 2015 Published: November 09, 2015

ABSTRACT

Signaling transducer and activator 3 (STAT3) and cancer stem cells (CSCs) have garnered huge attention as a therapeutic focus, based on evidence that they may represent an etiologic root of tumor initiation and radio-chemoresistance. Here, we investigated the high phosphorylation status of STAT3 (p-STAT3) and its correlation with self-renewal markers in head neck squamous cell carcinoma (HNSCC). Over-expression of p-STAT3 was found to have increased in post chemotherapy HNSCC tissue. We showed that blockade of p-STAT3 eliminated both bulk tumor and side population (SP) cells with characteristics of CSCs in vitro. Inhibition of p-STAT3 using small molecule S3I-201 significantly delayed tumorigenesis of spontaneous HNSCC in mice. Combining blockade of p-STAT3 with cytotoxic drugs cisplatin, docetaxel, 5-fluorouracil (TPF) enhanced the antitumor effect in vitro and in vivo with decreased tumor sphere formation and SP cells. Taken together, our results advocate blockade of p-STAT3 in combination with conventional chemotherapeutic drugs enhance efficacy by improving CSCs eradication in HNSCC.

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Research Papers:

STAT3 blockade enhances the efficacy of conventional chemotherapeutic agents by eradicating head neck stemloid cancer cell

Abstract