STAT3 blockade enhances the efficacy of conventional chemotherapeutic agents by eradicating head neck stemloid cancer cell.
STAT3 blockade enhances the efficacy of conventional chemotherapeutic agents by eradicating head neck stemloid cancer cell.
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STAT3 阻断可通过根除头颈干细胞样癌细胞来增强传统化疗药物的疗效。
DOI：
10.18632/oncotarget.5986
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发表时间：
2015-12-08
期刊：
影响因子：
--
通讯作者：
Sun ZJ
中科院分区：
文献类型：
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作者：
Bu LL;Zhao ZL;Liu JF;Ma SR;Huang CF;Liu B;Zhang WF;Sun ZJ
信号转导子和激活子3（STAT 3）和癌症干细胞（CSC）作为治疗焦点已经获得了巨大的关注，基于它们可能代表肿瘤起始和放射化学抗性的病因学根源的证据。在此，我们研究了头颈部鳞状细胞癌（HNSCC）中STAT 3（p-STAT 3）的高磷酸化状态及其与自我更新标志物的相关性。发现化疗后HNSCC组织中p-STAT 3的过表达增加。我们表明，阻断p-STAT 3在体外消除了具有CSC特征的大块肿瘤和侧群（SP）细胞。使用小分子S3 I-201抑制p-STAT 3显著延迟小鼠中自发性HNSCC的肿瘤发生。阻断p-STAT 3与细胞毒药物顺铂、多西他赛、5-氟尿嘧啶（5-fluorouracil，TPF）联合应用，可增强体内外的抗肿瘤作用，减少瘤球形成和SP细胞。总之，我们的结果主张阻断p-STAT 3与常规化疗药物组合通过改善HNSCC中的CSC根除来增强功效。
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.