复方苦参注射液对进展期直肠癌放疗患者Stat3 / HIF-1α通路作用的分子机制研究

Rectal cancer high incidence and the side effect with radiotherapy are always one of the difficult clinical problem.Compound matrine injection as anticancer and improve the effective traditional Chinese medicine preparation immunity has been widely applied in clinic.Based on attenuated efficiency found in the preclinical study of compound matrine injection on patients with advanced rectal cancer, we investigate the dynamic changes of Stat3 / HIF-1 αsignaling pathway and its downstream regulatory factor in serum and lesion of rectal carcinoma patients. At the same time, using the anaerobic cell culture model is further validated that Stat3 / HIF-1 αsignaling pathway in tumor radiosensitivity in the role and the possible molecular mechanism, to clarify the compound matrine injection through inhibition of NF- kappa beta, IL-8, C-myc, HIF-1 αto interfere with Stat3 / HIF-1 αsignaling pathways to enhance tumor radiosensitivity hypothesis, to investigate the mechanism of compound matrine attenuated synergistic molecular signal transduction in rectal cancer patients with radiotherapy, pathogenesis and prevention strategy in order to explore an advanced rectal cancer.

直肠癌的高发病率及作为主要临床治疗手段之一的放疗后副作用一直是困扰临床的难题之一。复方苦参注射液作为抗癌和提高免疫力的有效中药制剂已广泛应用于临床。本项目在前期临床研究中发现复方苦参注射液对进展期直肠癌放疗患者具有减毒增效的基础上，动态观察Stat3 / HIF-1α信号通路及其上下游调控因子的变化。同时，采用无氧细胞培养模型进一步验证阐明Stat3 / HIF-1α信号通路在增强肿瘤射线敏感性中的作用及其可能的分子机制，以阐明复方苦参注射液可能通过抑制NF-ΚΒ、IL-8、C-myc、HIF-1α来干扰Stat3 / HIF-1α信号通路来增强肿瘤射线敏感性的假说，探讨复方苦参注射液对直肠癌放疗患者减毒增效分子信号传导的机制，以期探寻进展期直肠癌的发病机制和防治新策略。

直肠癌的高发病率及作为主要临床治疗手段之一的放疗后副作用一直是困扰临床的难题之一。复方苦参注射液作为抗癌和提高免疫力的有效中药制剂已广泛应用于临床。在前期临床研究中发现复方苦参注射液对进展期直肠癌放疗患者具有减毒增效的基础上，本研究通过临床研究观察复方苦参注射液对直肠癌放疗患者疗效、毒副反应相关指标的变化，细胞实验验证Stat3 / HIF-1α信号通路在增强肿瘤射线敏感性中的可能作用，同时课题组进一步课采用网络药理学方法预测了苦参碱抗直肠癌作用机制，动物实验进行验证。本研究部分阐明复方苦参注射液抑制NF-Κ Β 、IL-8、C-myc、HIF-1α 干扰Stat3 / HIF-1α 信号通路来增强肿瘤射线敏感性的机制，为临床直肠癌治疗提供新的治疗依据。