琼玉膏调控Th/Treg平衡改善小鼠胰腺癌微环境的作用及机制研究

Pancreatic cancer continues to be an aggressive and highly lethal malignant disease, the patients is often shown as deficiency of Qi and yin or deficiency of spleen and Qi stagnation. Immune and inflammatory reaction induced by regulatory T cells Th/Treg was the essential feature of pancreatic cancer microenvironment, and these reactions play an important role in the initiation and aggravation in the pancreatic cancer. Qiongyu Gao originated from “Hong’s proved recipe collection” which written by Hong Zun, and this recipe can tonifying qi and yin and replenishing qi to invigorate the spleen. Our previous studies showed that Qiongyu Gao can suppress the lung carcinoma cells division and promote them to apoptosis. In order to investigate the therapeutical effects of Qiongyu Gao on pancreatic cancer, this study used Stat6-/- and ROR-γt-/- gene knockout mice to establish the pancreatic cancer animal model, and then further explore the roles and mechanism of Qiongyu Gao on therapy of pancreatic cancer. Observation of Th/Treg balance regulated by Qiongyu Gao on pancreatic cancer, the effects of pancreatic cancer microenvironment improved by Qiongyu Gao and the increasing effect and decreasing toxicity of Qiongyu Gao on chemotherapy of pancreatic cancer. Depending on all above studies, reveal the mechanism of Qiongyu Gao regulate the Th/Treg balance and tumor microenvironment, and evaluate the increasing effect and decreasing toxicity of Qiongyu Gao on chemotherapy of pancreatic cancer, and provide the scientific basis of Qiongyu Gao on therapy of pancreatic cancer.

胰腺癌持续成为高致死性疾病，患者在临床上表现为气阴亏虚、脾虚气滞等证候。调节性T细胞Th/Treg介导的免疫和炎症反应，是胰腺癌微环境的基本特征之一，在胰腺癌的发生发展中起着重要的作用。“琼玉膏”出自宋代洪遵《洪氏集验方》，能益气养阴、行气健脾。前期的研究发现，琼玉膏能增强化疗药物抑制肺癌细胞分裂、促进肺癌细胞凋亡的作用。本项目拟运用Stat6-/-和ROR-γt-/-基因敲除小鼠建立胰腺癌小鼠模型，分别采用琼玉膏和吉西他滨进行治疗，观察琼玉膏对胰腺癌小鼠的调节性T细胞Th/Treg的作用，对胰腺癌微环境的改善作用以及对胰腺癌化疗的骨髓造血功能影响和增效减毒作用。通过以上研究，揭示琼玉膏调控Th/Treg平衡和改善胰腺癌微环境的机制，评价琼玉膏对胰腺癌化疗的骨髓造血和增效减毒的作用，从而为琼玉膏辅助治疗胰腺癌提供科学依据。

胰腺癌持续成为高致死性疾病，患者在临床上表现为气阴亏虚、脾虚气滞等证候，治疗上宜采用“益气养阴”法为主。“琼玉膏”出自宋代洪遵《洪氏集验方》，是“益气养.阴”名方、并能行气健脾。前期的研究发现，琼玉膏能增强化疗药物抑制肺癌细胞分裂、促进肺癌细胞凋亡的作用。本项目拟运用Stat6-/-和ROR-γt-/-基因敲除小鼠建立胰腺癌小鼠模型，分别采用琼玉膏和吉西他滨进行治疗，观察琼玉膏对胰腺癌小鼠的调节性T细胞Th/Treg的作用，对胰腺癌微环境的改善作用以及对胰腺癌化疗的骨髓造血功能影响和增效减毒作用。通过以上研究，揭示琼玉膏调控Th/Treg平衡和改善胰腺癌微环境的机制，评价琼玉膏对胰腺癌化疗的骨髓造血和增效减毒的作用，从而为琼玉膏辅助治疗胰腺癌提供科学依据。