化疗作为胃癌综合治疗重要组成部分，药物敏感性显著影响预后。HMGB1及线粒体功能均可影响化疗药物敏感性，HMGB1是线粒体功能重要调控因子，但“HMGB1-线粒体”作用通路对化疗敏感性的影响和机制，并不明确；新型HMGB1抑制剂的筛选，明确其对胃癌化疗药物敏感性的影响，十分必要。前期研究证实：胃癌存在HMGB1过表达，与预后相关；干扰HMGB1表达，可影响线粒体功能。本课题以胃癌切入点，研究：①HMGB1表达与定位对胃癌化疗药物敏感性的影响。②HMGB1对线粒体功能的调控作用，及其分子机制。③“HMGB1-线粒体”作用通路在胃癌药物敏感性调控中的地位和精确分子机制。④新型HMGB1抑制剂TSD对胃癌细胞生物学行为，包括化疗药物敏感性的影响。本课题将深入胃癌化疗药物敏感性的HMGB1、线粒体相关机制探索，明确新型HMGB1抑制剂的作用，益于胃癌治疗研究。

Chemotherapy is an integral part of the combined treatment of gastric cancer. The anti-cancer sensetivity significantly affect the prognosis. HMGB1 and the integrity of mitochondrial function play key or central roles in the emergence and development of cancer, including gastric cancer. More and more evidences show that they also influence the sensitivity of anti-tumor drugs. The recent studies have identified that HMGB1 was an important regulator of mitochondria, and cross-talk with mitochondria in the related mechanisms. But it is not evident that HMGB1 and mitochondria play their relatively independent roles, or have the common pathway. The further study was necessary to show the effect and mechanism of “HMGB1-mitochondria” regulation pathway on the sensitivity of anti-cancer drugs, especially in gastric cancer. Based on our preliminary work, we present the study to reveal the biological functions and molecular mechanisms of HMGB1 on the maintenance of mitochondria architecture and function integrity, and their effect on the sensitivity of anti-cancer drugs. The main research contents include: 1) The effect of HMGB1 on the sensitivity of chemotherapic drugs to gastric cancer. 2) The effect and mechnism of HMGB1 on the function and architecture of mitochondria. 3) The effect and mechnism of "HMGB1-mitochondria" pathway on the sensitivity of anti-cancer drugs. 4)The effect of a novel HMGB1 inhibitor, TSD, on the biological behaviors of gastic cancer cells, including the sensitity of anti-cancer drugs. The associated study will reveal the biological functions and the mechanism HMGB1 in the maintenance of mitocondria integrity, deepen the mechanism study associated with HMGB1 and mitochondria on the sensitivity of the anti-cancer drugs, and accelerate the study of the novel inhibitor targeting HMGB1.