LP1蛋白PI3K-III样功能域诱导肺癌细胞程序性死亡的分子机制研究

With the less side effect and powerful function, the biological treatment of tumor has significant advantages in cancer treatment. At present, the molecular targeted therapy is becoming the new hotspot in addition to immune therapy, gene therapy and anti-angiogenesis therapy in this filds. A kind of antitumor mycoprotein was found at the first time. We named it as Latcripin-1(LP1). In order to clarify the mechanism of its inducing apoptosis in lung cancer cells, we plan to obtain purified Latcripin-1 protein PI3K-Ⅲ functional domain peptides by the Pichia pastoris eukaryotic expression and purification systems. Flow cytometry and other methods will be used to detect the biological influence of domain PI3K-Ⅲ to lung cancer cell. Real-Time PCR and Western blot will be used to analyze the molecules' expression and change during the course of type I programmed cell death(apoptosis) or type II programmed cell death (autophagy)in lung cancer cells. Combining with Pull-down technology, we try to elucidate the molecular mechanism of protein LP1 PI3K-Ⅲ functional domain to lung cancer cells. All of these will develop a new field in finding the antitumor polypeptide drugs.

肿瘤的生物治疗以不良反应小、疗效显著等优点在肿瘤治疗方面具有独到之处。目前，分子靶向治疗正成为除免疫治疗、基因治疗和抗血管生成治疗外的又一肿瘤生物治疗热点所在。本课题组前期工作首次发现了香菇菌C91-3中具有诱导人肺癌细胞程序性死亡功能的特异性蛋白-LP1，该蛋白诱导细胞程序性死亡具有肿瘤细胞选择性。深入研究发现，其包含三级结构极为特别的PI3K-Ⅲ样功能域，此类功能域在某些肿瘤细胞自噬过程中发挥重要作用，而对人肺癌细胞的作用机制尚未明确。本课题在获得高纯度PI3K-Ⅲ样功能域的基础上，检测其对肺癌细胞生物学行为的影响；利用自噬与凋亡通路高通量筛选系统研究此功能域引起肺癌细胞程序性死亡过程中相关分子的表达及变化，从而阐明LP1蛋白PI3K-Ⅲ样功能域诱导肺癌细胞程序性死亡的分子机制，为寻找毒副作用小、靶向作用强的肿瘤生物治疗多肽类药物开辟新途径。

肿瘤的生物治疗以不良反应小、疗效显著等优点在肿瘤治疗方面具有独到之处。目前，分子靶向治疗正成为除免疫治疗、基因治疗和抗血管生成治疗外的又一肿瘤生物治疗热点所在。本课题组前期工作首次发现了香菇菌C91-3中具有诱导人肺癌细胞程序性死亡功能的特异性蛋白-LP1，该蛋白诱导细胞程序性死亡具有肿瘤细胞选择性。深入研究发现，其包含三级结构极为特别的PI3K-Ⅲ样功能域，此类功能域在某些肿瘤细胞自噬过程中发挥重要作用。本课题在获得高纯度PI3K-Ⅲ样功能域的基础上，检测其对胃癌细胞生物学行为的影响；利用自噬与凋亡通路高通量筛选系统研究此功能域引起胃癌细胞程序性死亡过程中相关分子的表达及变化，从而阐明LP1蛋白PI3K-Ⅲ样功能域诱导胃癌细胞程序性死亡的分子机制，为寻找毒副作用小、靶向作用强的肿瘤生物治疗多肽类药物开辟新途径。