西黄丸为传统抗癌良药，与化疗药联用可防止肿瘤出现耐药与复发，但其分子机制有待阐明。最近国外研究表明，利用COX-2抑制剂抗炎治疗可抑制肿瘤干细胞，延缓肿瘤出现耐药、复发和转移。这对研究我国传统抗癌中药的作用机制进行了重要提示。我们的前期结果显示，西黄丸可显著降低因化疗药诱导升高的肿瘤干细胞标志物。同时国外报道，西黄丸的成分可抑制COX-2/PGE2等重要炎症信号通路。因此，本研究旨在以炎症信号通路为切入点，通过分子、细胞、动物多层次实验研究，分析西黄丸通过干预炎症信号通路而抑制肿瘤干细胞的分子机制，揭示其对COX-2/PGE2及其下游分子网络的调控机理，证实西黄丸通过解毒散结的抗炎作用抑制肿瘤干细胞，从而实现延缓肿瘤耐药、复发和转移的功效。本研究将首次从肿瘤干细胞的角度探讨西黄丸的作用机制，对阐明西黄丸防止肿瘤耐药、复发和转移的分子机制有重大意义，为进一步开发传统中药提供重要思路。

Xihuang pill is a complementary drug used for tumor treatment since the period of ancient China. Combined with chemotherapy drugs, it can prevent drug resistance and relapse of tumor. But the molecular mechanisms remain to be clarified. Recent foreign studies showed that COX-2 inhibitors, which were anti-inflammatory drugs, could suppress cancer stem cells and avoided drug resistance, recurrence and metastasis of tumor. This is an important clue to study the mechanisms of traditional Chinese drugs which have anti-tumor effects. Results in our labs showed that Xihuang pill down-regulated cancer stem cell markers, which were up-regulated after chemotherapy drug treatment. Meanwhile, foreign studies showed that ingredients from Xihuang pill could inhibit important inflammatory signaling pathways such as COX-2/PGE2. Therefore, by in vivo and in vitro experiments, this study aims to clarify the molecular mechanism of inhibiting cancer stem cells of xihuang pill, reveal its mechanisms of regulating COX-2/PGE2 and its downstream molecular network, and prove its detoxification and anti-inflammatory effects, which contributes to delaying cancer drug resistance, recurrence and metastasis of the tumor. It is the first time to study the molecular mechanism of XiHuang pill from the point of view of cancer stem cell. It is of great importance to know the molecular mechanisms of how XiHuang pill prevents tumor drug resistance, recurrence and metastasis. And this study would also provide a new perspective for the development of traditional Chinese medicine in the future.

本课题旨在阐明传统抗癌良药西黄丸与化疗药物联合应用减少肿瘤耐药发生和转移的分子机制。研究发现，西黄丸可显著降低因紫杉醇刺激而升高的PGE2分泌，并通过PGE2下游调控的重要蛋白ERK、STAT3及其磷酸化水平的差异性分析，进一步证明西黄丸可抑制该信号通路。同时，利用紫杉醇模拟化疗，建立富集肿瘤干细胞模型。通过评估肿瘤干细胞标志物、肿瘤球形成以及PGE2下游重要耐药相关基因（VEGF、IL-8等）的表达变化，证实了西黄丸可抑制COX-2下游的PGE2炎症信号通路并同时抑制肿瘤干细胞表型，实现减少耐药和转移。完成转录组研究，获得了一批包括愈伤迁移基因在内的可能受西黄丸调控的基因。本研究利用现代生物学“炎症-肿瘤干细胞模型”为西黄丸的中医“解毒散结”治疗肿瘤病机带来新的理解，为探索西黄丸在未来更好地应用于临床提供重要支持。