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

被引：42

作者：

Bu, Lin-Lin ^{[1
,2
,3
]}

Zhao, Zhi-Li ^{[1
,2
]}

Liu, Jian-Feng ^{[1
,2
]}

Ma, Si-Rui ^{[1
,2
]}

Huang, Cong-Fa ^{[1
,2
]}

Liu, Bing ^{[1
,2
,3
]}

Zhang, Wen-Feng ^{[1
,2
,3
]}

Sun, Zhi-Jun ^{[1
,2
,3
]}

机构：

[1] Minist Educ, State Key Lab Breeding Base Basic Sci Stomatol, Wuhan, Peoples R China

[2] Minist Educ, Key Lab Oral Biomed, Wuhan, Peoples R China

[3] Wuhan Univ, Dept Oral Maxillofacial Head Neck Oncol, Sch & Hosp Stomatol, Wuhan 430072, Peoples R China

来源：

ONCOTARGET | 2015年 / 6卷 / 39期

基金：

中国国家自然科学基金;

关键词：

STAT3; head neck squamous cell carcinoma; cancer stem cell; S3I-201; chemotherapy; DRUG-RESISTANCE; DECOY OLIGONUCLEOTIDE; SIGNAL TRANSDUCERS; ANTITUMOR EFFICACY; GENE-EXPRESSION; SIDE POPULATION; ACTIVATION; INHIBITION; CISPLATIN; TRANSCRIPTION;

D O I：

10.18632/oncotarget.5986

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 [肿瘤学];

摘要：

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.

引用

页码：41944 / 41958

页数：15

共 53 条

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