健脾复方上调小分子多肽CDP3逆转结直肠癌耐药的机制研究

化疗耐药是结直肠癌（CRC）患者预后差的重要原因之一，尚缺乏有效逆转策略。健脾复方是我们课题组研制的治疗CRC的中药复方，在体动物及临床展现了良好的CRC治疗效果。进一步发现，健脾复方抑制HCT116/5-FU耐药株的增殖和迁移、促进凋亡；多肽组学分析发现，健脾复方促进HCT116/5-FU耐药株功能未知多肽CDP3高表达，质谱鉴定出CDP3可结合NF-κB p65并降低其磷酸化水平。因此我们提出假说：健脾复方可通过上调CDP3结合NF-κB通路而发挥其逆转5-FU的耐药作用。研究拟在不同CRC化疗耐药细胞和异种肿瘤动物模型上，系统评估健脾复方通过上调多肽CDP3抑制CRC细胞耐药的生物学效应；以挽救实验策略，系统论证健脾复方由多肽CDP3调控NF-kB通路逆转CRC耐药性的机制。多肽组学探讨中药复方逆转CRC耐药机制未见报道，具有创新性。若受资助，可为结直肠癌的化疗药物抵抗提供新思路。

Chemotherapy resistance of colorectal cancer (CRC) is one of the important reasons for poor prognosis of CRC patients, and there is no effective reversal strategy. Jianpi compound is a traditional Chinese medicine compound developed by our research group for the treatment of CRC, which shows good therapeutic effect in vivo animals and clinical trials. Furthermore, it was found that Jianpi compound could inhibit the proliferation and migration, and promote apoptosis of HCT116 / 5-FU resistant cells; polypeptide omics analysis showed that Jianpi compound could promote the high expression of function-unknown polypeptide CDP3 in the HCT116/5-FU resistant cells, and the mass spectrum analysis showed that CDP3 could bind to NF-κB. Therefore, we provide the “hypothesis” that Jianpi compound could reverse 5-FU resistance by upregulating the binding of CDP3 to NF-κB pathway. In the proposed study, we will systematically evaluate the biological effect of Jianpi compound in inhibiting the drug resistance of CRC cells by upregulating the polypeptide CDP3 in different CRC chemoresistant cells and Xenogeneic tumor models, and to systematically demonstrate the mechanism of Jianpi compound in reversing the drug resistance of CRC by regulating the NF-κB pathway by polypeptide CDP3 through rescue experimental strategy. To date, there is no report about the mechanism of traditional Chinese medicine compound reversing CRC drug resistance by polypeptide omics, which is innovative. If founded, the findings of the study potentially provide novelty approaches for chemoresistance of colorectal cancer.