期刊
ONCOTARGET
卷 6, 期 39, 页码 41944-41958出版社
IMPACT JOURNALS LLC
DOI: 10.18632/oncotarget.5986
关键词
STAT3; head neck squamous cell carcinoma; cancer stem cell; S3I-201; chemotherapy
资金
- National Natural Science Foundation of China [81072203, 81272963, 81472528, 81272964, 81472529, 81402241]
- program for new century excellent talents in university, Ministry of Education of China [NCET-13-0439]
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). Overexpression 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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