生物活性肽联合奥沙利铂下调TPX2治疗胃癌增敏分子作用机制研究

批准号:
81960560
项目类别:
地区科学基金项目
资助金额:
34.0 万元
负责人:
苏秀兰
依托单位:
学科分类:
肿瘤治疗抵抗
结题年份:
2023
批准年份:
2019
项目状态:
已结题
项目参与者:
苏秀兰
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中文摘要
联合用药是肿瘤治疗中降低毒副作用和增强化疗效果的重要手段之一。前期研究发现,奥沙利铂联合生物活性肽(BAP)不但可以明显降低奥沙利铂的使用量,而且减轻副作用,但是具体分子调控机理尚未阐明。预实验结果显示联合作用与TPX2的表达下调相关。TPX2与胃癌发生和发展密切相关,是抗癌药物研发的重要靶点之一。据此提出科学假设:BAP协同奥沙利铂治疗胃癌可起到减毒增敏作用;分子机理可能涉及TPX2的表达下调,从而影响了所介导的PI3/AKT信号通路,影响了下游靶分子Aurora A以及细胞周期进程,最终抑制胃癌的发生与发展。项目以临床样本、细胞实验、动物体内实验和生物信息学分析等方法解释BAP联合奥沙利铂减毒增敏作用,阐明联合用药调控TPX2蛋白表达从而抑制胃癌发生发展的分子机制,揭示BAP联合奥沙利铂在胃癌治疗过程中潜在应用价值,为胃癌靶向联合治疗提供新思路。
英文摘要
The drug combination is one of the excellent treatment methods to reduce toxic side effects and provide a positive impact on the effect of chemotherapy. Our previous study has found that oxaliplatin combined with bioactive peptide (BAP) is not only significantly reduce the consumption of oxaliplatin but also minimise side effects. However, the molecular mechanism is still unclear. Pre-experimental results suggest that this effect may be associated with the down-regulation of TPX2 expression. TPX2 is one of the critical targets for the development of anticancer drugs due to is closely related to the occurrence and development of gastric cancer. We proposed a hypothesis that BAP combined with oxaliplatin in the treatment of gastric cancer can play a role in the toxicity reduction and improving the therapeutic efficiency of oxaliplatin;The molecular mechanism may be down-regulated by the expression of TPX2, which affects the mediated PI3/AKT signaling pathway, the downstream target molecule Aurora A and cell cycle progression, and finally suppresses the occurrence and development of gastric cancer. This research combined the use of clinical samples, cell experiments, in vivo experiments in animals and bioinformatics analysis to explain the molecular mechanism of BAP combined with oxaliplatin for toxicity reduction and therapeutic efficiency improvement. In particular, it was demonstrated that this drug combination method down-regulated TPX2 protein expression and thereby inhibits the development of gastric cancer. The potential application value of BAP combined with oxaliplatin in the treatment of gastric cancer was clarified, which provided a promising idea for targeted therapy of gastric cancer.
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专利列表
Effect of animal-sourced bioactive peptides on the in vitro development of mouse preantral follicles
DOI:10.1186/s13048-020-00695-8
发表时间:2020-09
期刊:Journal of Ovarian Research
影响因子:4
作者:Gang Liu;Shubin Li;Jinyu Ren;Chunyu Wang;Yaxuan Zhang;X. Su;Yanfeng Dai
通讯作者:Gang Liu;Shubin Li;Jinyu Ren;Chunyu Wang;Yaxuan Zhang;X. Su;Yanfeng Dai
DOI:10.3892/or.2019.7406
发表时间:2020-01-01
期刊:ONCOLOGY REPORTS
影响因子:4.2
作者:Xu, Yanan;Li, Xian;Su, Xiulan
通讯作者:Su, Xiulan
DOI:DOI 10.7717/peerj.14384
发表时间:2023
期刊:Peer J
影响因子:--
作者:Yanan Xu;Wen J;Han W;Yan J;Jia W;Su X
通讯作者:Su X
DOI:10.1007/s13402-022-00666-9
发表时间:2022-06
期刊:CELLULAR ONCOLOGY
影响因子:6.6
作者:Zhang, Le;Su, Xiulan
通讯作者:Su, Xiulan
DOI:10.1016/j.cryobiol.2020.08.007. Epub 2020 Aug 26.
发表时间:2020
期刊:Cryobiology
影响因子:--
作者:Gang Liu;Bin Pan;Shubin Li;Jingyu Ren;Biao Wang;Chunyu Wang;Xiulan Su 通讯;Yanfeng Dai 通讯
通讯作者:Yanfeng Dai 通讯
生物活性肽ACBP介导miRNA调节胃癌干细胞作用机制及功能研究
- 批准号:81660468
- 项目类别:地区科学基金项目
- 资助金额:38.0万元
- 批准年份:2016
- 负责人:苏秀兰
- 依托单位:
离子通道基因TSC及CLCNK与内蒙古地区蒙古族原发性高血压家系的关联研究
- 批准号:81260058
- 项目类别:地区科学基金项目
- 资助金额:47.0万元
- 批准年份:2012
- 负责人:苏秀兰
- 依托单位:
生物活性肽抑制胃癌干细胞的作用和机制研究
- 批准号:81160254
- 项目类别:地区科学基金项目
- 资助金额:50.0万元
- 批准年份:2011
- 负责人:苏秀兰
- 依托单位:
抗癌活性肽基因克隆与原核表达及抗肿瘤作用
- 批准号:30860327
- 项目类别:地区科学基金项目
- 资助金额:26.0万元
- 批准年份:2008
- 负责人:苏秀兰
- 依托单位:
抗癌活性肽对胃癌细胞周期及凋亡的调控
- 批准号:30460146
- 项目类别:地区科学基金项目
- 资助金额:19.0万元
- 批准年份:2004
- 负责人:苏秀兰
- 依托单位:
国内基金
海外基金
