抗寄生虫药物酒石酸锑钾抗肿瘤血管新生作用及其机理研究

非小细胞肺癌的生长和转移与血管新生密切相关，靶向肿瘤血管新生已成为非小细胞肺癌临床治疗的重要策略。但目前的抗血管生成药物对非小细胞肺癌晚期患者疗效不显著，亟需开发新的候选药物。老药新用即老药临床新用途的开发，是一种快速发现新药的有效途径。我们通过筛选老药分子库，发现抗寄生虫药物酒石酸锑钾可抑制内皮细胞的增殖并减少促血管生成因子诱导的迁移, 以及破坏内皮细胞二维管状结构的形成。初步机理研究显示酒石酸锑钾可显著下调若干受体酪氨酸激酶的磷酸化水平。基于以上工作基础，本项目拟利用小鼠血管新生模型和小鼠荷瘤模型，结合体外分子和细胞模型，揭示酒石酸锑钾的抗肿瘤血管新生活性及其分子机制，以期为其临床新适应症的应用提供科学依据。

The growth and metastasis of non-small cell lung cancer (NSCLC) depend on angiogenesis, and inhibition of tumor-related angiogenesis has become an important strategy for NSCLC therapy. While currently, there are no effective drugs to improve the survival of advanced stage NSCLC, so it is still very necessary looking for new drug candidates. Drug repurposing may offer a faster and cheaper way to new medicine since those drugs have already been tested for their safety. We screened our old drugs library, and found potassium antimony tartrate (PAT) which was used in the treatment of schistosomiasis and leishmaniasis can inhibit proliferation of endothelial cells, decrease migration induced by angiogenesis factors, and damage tube formation of endothelial cells. Our studies also showed that PAT can significantly decrease some receptor tyrosine kinase phosphorylation. Based on our previous work, we intend to use the tumor growth and angiogenesis in a mouse model, molecular and cell-based experiments, find the mechanism for the anti-tumor and anti-angiogenic activity of PAT, and finally figure out the potential clinical application of PAT.