阿司匹林在化疗诱导的结肠肿瘤干细胞富集及耐药中的干预作用及机制研究

Chemotherapy-induced enrichment of cancer stem cells (CSCs) is one of the main failure reasons of colon cancer treatment. Inflammatory cytokine IL-6 and activation of NF-κB and STAT3 signaling pathways may play an important role in maintenance and chemotherapy resistance of CSCs. Our preliminary results shows that chemotherapy-induced enrichment of colon CSCs may be related with chemotherapy-induced inflammation and that aspirin, a non-specific anti-inflammatory drug, may inhibit self-renewal of CSCs by its anti-inflammatory effect. According to domestic and foreign research reports and our preliminary study results, we hypothesize that chemotherapy-induced inflammation and activation of IL-6/NF-κB/STAT3 signaling pathway is one of the most important reasons of enrichment and chemotherapy resistance of CSCs, while aspirin may be able to reverse this effect. Therefore, we intend to explore the role of aspirin in the inhibition of colon CSCs and underlying mechanisms to find the effective and economical method in the prevention and treatment of colon cancer; meanwhile, we try to investigate aspirin as a sensitizer to improve the sensitivity of CSCs to chemotherapeutic drugs, reverse the chemotherapy-induced enrichment of CSCs, and the underlying mechanisms, providing the theoretical and experimental foundation for future clinical application.

化疗诱导的肿瘤干细胞富集是结肠癌治疗失败的主要原因之一，但机制仍不清楚。炎症因子IL-6及其激活的炎症信号通路NF-κB 和STAT3在肿瘤干细胞的维持与治疗抵抗中可能起着重要的作用。我们前期的研究结果表明，化疗诱导的结肠肿瘤干细胞富集可能与化疗诱导的炎症有关，非特异性抗炎药阿司匹林可能通过其抗炎作用抑制结肠肿瘤干细胞的自我更新。根据国内外研究报导及我们的前期研究结果，我们推测化疗药物诱导的炎症及活化的IL-6/NF-κB/STAT3信号通路可能是结肠肿瘤干细胞富集、耐药的重要原因，而阿司匹林可能能逆转这种效应。因此，我们探讨阿司匹林在抑制结肠肿瘤干细胞中的作用及其机制，期望为临床结肠肿瘤的防治找到经济有效的方法；同时，探明阿司匹林作为药物增敏剂提高结肠肿瘤干细胞对化疗药物的敏感性、逆转化疗诱导的结肠肿瘤干细胞富集的可行性及机制，为将来二者联合应用临床提供理论及实验基础。