枸杞多糖通过PMI增加结直肠癌干细胞对奥沙利铂敏感性的研究

枸杞多糖（LBP）可以影响结肠癌细胞的细胞周期而抑制肿瘤生长，我们前期的工作已证实LBP与奥沙利铂联合抑制肿瘤生长比单用奥沙利铂更明显，磷酸甘露糖异构酶（PMI）与肿瘤干细胞亚群相关并参与化疗抵抗，但其耐药机制尚未明确。以往研究发现，PMI对甘露糖的新陈代谢起重要的作用，PMI的缺失抑制糖酵解，导致细胞凋亡增加。LBP是否通过PMI影响结直肠癌干细胞的增殖与凋亡参与肿瘤细胞对化疗药敏感性的调控？拟以结直肠癌细胞和临床标本为研究对象，采用全基因组芯片、信号通路高通量检测蛋白芯片、免疫组化、CRISPR-Cas9等方法及NOD-SCID小鼠移植瘤PDX模型，探讨PMI在结肠癌中的作用和耐药相关性；LBP对结直肠癌的“干性”以及对化疗敏感性的影响及机制研究。研究结果将对枸杞作为药食同源的资源及其抗肿瘤作用提供新的认识，为临床新辅助化疗病人寻找有效的逆转耐药途径提供新的、有力的实验依据。

Lycium barbarum polysaccharide (LBP) can affect the cell cycle of colon cancer cells and inhibit tumor growth. The results of the present study have confirmed that LBP combined with oxaplatin inhibits tumor growth more significantly than oxaplatin alone. PMI is expressed in CSCs from human colorectal tumors and contributes to multi-drug resistance during chemotherapy. However, additional studies are needed to elucidate the mechanisms underlying the drug resistance.Based on recent evidence that MPI loss induces p53, and identifies MPI as a novel regulator of p53 and Warburg metabolism. In this study, we first investigated the role of PMI in colon cancer stem cells. We also evaluated Lycium barbarum polysaccharides increased the sensitivity of oxaliplatin in colorectal cancer stem cells. Gene chip, Signal pathway protein array chip and Clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR- associated (Cas) 9 technology are using in LS174T colon cancer cell line and NOD-SCID mouse in patient-derived xenografts model for colorectal carcinomas. This study demonstrated that the mechanism of Lycium barbarum polysaccharides increased the sensitivity of oxaliplatin in colorectal cancer stem cells through regulation of PMI . In conclusion, this information might be useful for future studies aiming to improve the therapeutic strategies so that new drugs can be invented that may target and eliminate the CSCs responsible for tumor recurrence.