外源性多胺诱导肿瘤细胞自噬与凋亡的微量热学研究

体内多胺水平与肿瘤细胞的自噬和凋亡密切相关，两者的交互作用机制是亟待解决的重要科学问题。本项目选择人宫颈癌细胞HeLa作为模型细胞系，以不同种类不同浓度的多胺为处理药物，联合多胺抑制剂和自噬抑制剂；用微量热方法研究肿瘤细胞在不同药物环境中自噬、凋亡的热谱曲线，建立热、动力学模型，解析热、动力学参数，从能量角度探讨细胞自噬、凋亡的变化规律；用显微、光谱和细胞生物学等方法检测细胞自噬、凋亡的形态和物质的变化；从形态、能量和物质变化等角度综合分析自噬、凋亡发生及各阶段的变化规律。结合多胺的介质效应及其与相关DNA、蛋白质等生物大分子的相互作用研究，探讨多胺诱导肿瘤细胞自噬和凋亡的交互作用机制。研究成果有助于进一步揭示肿瘤等疾病的发生、发展机制，对肿瘤等疾病的治疗具有重要意义。

The level of polyamines in vivo is closely related to autophagy and apoptosis of tumor cell, and the interaction mechanism between autophagy and apoptosis is an important scientific problem to be solved. In this project，the human HeLa cells of cervical cancer will be chosen as the model cell lines. The targeted drugs, such as different types of polyamines, inhibitors of polyamine and autophagy, will be used to regulate the autophagy and apoptosis of HeLa cells. The microcalorimetric method will be used to determine the thermal spectra for the autophagy and apoptosis of HeLa cells with the existence of different drugs. The thermokinetic model will be established, and the corresponding thermodynamic parameters will be calculated to explore variation of autophagy and apoptosis from the energy point of view. Microscopy, spectroscopy and cell biology methods will be used to observe the cell morphology and material change of autophagy and apoptosis. The development process of autophagy and apoptosis will be analyzed with the combination of cell morphology, energy change and material change. Combined with the medium effect of polyamines and the interactions between polyamines and DNA, proteins，the interaction mechanism of autophagy and apoptosis for tumor cells induced by polyamines is explored. The investigations are expected to reveal mechanisms of occurrence and development of cancer，and therefore are of great significance for the treatment of cancer.