异硫氰酸苯乙酯（PEITC）抑制结肠癌转移及其分子机制的研究

Metastasis and tumor cell self-renewal is the main cause of failure in colon cancer treatment. However, the exact mechanism is not fully understood. Our previous studies indicated that PEITC (β-phenylethyl isothiocyanate), as an extract from cruciferous antioxidants, can effectively reverse platinum-resistance of lung and colon cancer cells, in the meantime, we found that these platinum-resistance cells have more strong capacity of invasion. Whether and how PEITC suppressing colon cancer metastasis remains to be elucidated. Recent preliminary experiments showed that PEITC can reverse early invasion and metastasis of colon cancer, may also can inhibit the Wnt/β-Catenin and HGF-MET/Akt signaling pathways. The current project intends to reveal whether PEITC suppress colon cancer metastasis through blocking Wnt/β-Catenin and HGF-MET/Akt pathways, by a series of methods in platinum-resistant colon cancer cells model. Finally, combining with animal tissue samples, the study would validate the molecular mechanisms of PEITC inhibiting cancer metastasis and cancer stem cell self-renewal. This project may help provide a new theoretical basis for PEITC used in treatment of colon cancer.

结肠癌转移及肿瘤细胞自我更新是结肠癌治疗失败的最重要因素之一，但具体机制尚未完全阐明。我们的前期研究发现，PEITC（β-phenylethyl isothiocyanate，异硫氰酸苯乙酯），一种从十字花科中提炼出来的抗氧化剂，能有效逆转肺癌及肠癌细胞的铂类耐药，同时发现这些铂类耐药的细胞具有更强的侵袭能力，PEITC是否以及如何抑制肠癌的侵袭转移的分子机制尚待阐明。近期的预实验结果显示，PEITC可以影响癌症早期浸润转移，并能抑制Wnt/β-Catenin 、HGF-MET/Akt信号通路。本项目拟以铂类耐药的肠癌细胞为模型，通过一系列方法，明确PEITC是否通过Wnt/β-Catenin 、HGF-MET/Akt通路抑制转移；并结合动物组织样本，深层次解析PEITC抑制结直肠癌转移及肿瘤细胞自我更新的分子机制，为PEITC用于结肠癌的治疗提供新的理论依据。

针对异硫氰酸苯乙酯（PEITC）是抑制结肠癌转移的关键因素，我们在原有的研究基础上进一步探究发现PEITC通过调控一系列基因的表达从而抑制结肠癌发生发展的分子机制，并找到及验证了相关的重要分子。. 在此基础上，我们有以下重大发现： 解析了JADE3促进肠癌细胞肿瘤干性和和成瘤能力的分子机制，为肠癌的临床治疗提供了潜在的治疗靶点；我们研究发现HMMR在胃癌耐药组织中高表达，并与胃癌患者的总生存率、五年无复发生存率以及疾病进展相关。HMMR可以通过增强肿瘤细胞干性及诱导EMT进而引起胃癌化疗耐药。由此得出结论：肿瘤细胞干性调控在致瘤性方面发挥着重要作用；肿瘤干细胞及上皮间质转化（EMT）在肿瘤耐药方面发挥着重要作用。