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


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.

SUBMITTER: Bu LL 

PROVIDER: S-EPMC4747200 | biostudies-literature | 2015 Dec

REPOSITORIES: biostudies-literature

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

Bu Lin-Lin LL   Zhao Zhi-Li ZL   Liu Jian-Feng JF   Ma Si-Rui SR   Huang Cong-Fa CF   Liu Bing B   Zhang Wen-Feng WF   Sun Zhi-Jun ZJ  

Oncotarget 20151201 39


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 t  ...[more]

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