沉默STAT3增强SNX-2112诱导食管癌干细胞样细胞凋亡的作用机制研究

研究表明，肿瘤干细胞是肿瘤研究的重点。热休克蛋白90是潜在的抗肿瘤靶点。申请人博士阶段一直从事食管癌干细胞的靶向研究，前期博士阶段研究发现：①采用无血清培养的方法从食管癌细胞获得食管癌干细胞样的细胞；②经分析，该食管癌干细胞样细胞高表达Nanog、Sox2、Bmi1、STAT3等干性因子；③慢病毒沉默STAT3抑制该肿瘤干细胞样细胞增殖；④前期研究基础表明， Hsp90抑制剂SNX-2112具有良好的抗肿瘤能力，如肝癌、黑色素瘤、白血病等肿瘤细胞生长的能力。基于此，本课题拟以STAT3与SNX-2112的药效为切入点，我们推测，①沉默STAT3协同增强SNX-2112抑制食管癌干细胞样细胞增殖；②在小鼠体内实验，二者联合作用同样具有抗食管癌干细胞样细胞生长的效果。本课题将为阐明沉默STAT3增强SNX-2112抑制食管癌干细胞样细胞增殖提供依据，也为食管癌的临床治疗提供指导方向与治疗策略。

Many studies indicate that cancer stem cells (CSCs) play an important part in treating patients. Heat shock protein 90 is a potential anti-tumor target. Our applicants have been engaged in the study of esophageal cancer stem cells. In the phase of my doctor study we found that the esophageal cancer stem-like cells (ECSLCs) were isolated using serum-free suspension media to form spheres. The ECSLCs were characterized by qPCR and flow cytometry and these analysis demonstrated that Nanog, Sox2, Bmi1 and STAT3 were over-expressed in the ECSLCs. And slience of STAT3 inhibited the proliferation of ECSLCs. Moreover, Our former studies demonstrated that Hsp90 inhibitor SNX-2112 has strong anti-tumtor capacity, such as hepatocellular carcinoma, melanoma and leukemia cells. Base on these studies, we are going to study synergistic efficiacy of SNX-2112 with slience of STAT3. We intend to sudy whether SNX-2112 with slience of STAT3 synergistically induce apoptosis of ECSLCs. In addition, it will be confirmed whether SNX-2112 with slience of STAT3 combination have synergistic anti-tumor effect. These studies will provide strong evidence for the esophageal cancer therapeutic potential of the combination of SNX-2112 and slience of STAT3.