中文摘要
青蒿素B系中药黄花蒿中抗肿瘤活性成分。缝隙连接蛋白(Cx)具肿瘤抑制因子特性,能介导顺铂在肿瘤和非肿瘤细胞中的差异性积累,是极具潜力的抗肿瘤靶点。一线抗肿瘤药物顺铂对肿瘤细胞有着强大杀伤作用但严重的毒副作用成为限制其应用的瓶颈问题。我们前期研究发现:青蒿素B能协同顺铂抑制肺癌细胞的增殖且能改变肺癌细胞中Cx的表达及缝隙连接(GJ)功能,提示其对顺铂抗肺癌方面可能具有“增效减毒”作用且与Cx有关。为解决此科学问题,本项目拟在前期工作基础上,进行如下研究:(1)全面评价青蒿素B对顺铂抗肺癌的“增效减毒”作用;(2)确认青蒿素B“增效减毒”作用是否由Cx介导;(3)探究青蒿素B对Cx及GJ调控的相关信号通路。本项目系国内外首次基于Cx靶点对青蒿素B在抗肿瘤方面“增效减毒”作用机制进行研究,其结果可为青蒿素B的“增效减毒”作用给予科学阐释,并为拓展青蒿素类活性成分新用途提供科学资料。
英文摘要
Artemisinin B is one kind of anti-tumor active ingredient from Artemisia annua. Connexin (Cx) possesses tumor suppressor properties and can be a great potential target for cancer therapy. Cisplatin (DDP) is an antitumor drug in first-line therapy for cancer and can be differentially accumulated in tumor and non-tumor cells, which may be mediated by Cx. DDP has a strong cytotoxic effect on cancer cells, but severe side effects limit its clinical application. In the previous study, we found that Artemisinin B increased the cytotoxicity of DDP, up-regulated expression of Cx and enhanced the function of gap junction (GJ) in lung cancer cells, suggesting that it may have the synergism and detoxication effects in the treatment of lung cancer. To explore of the mechanism of synergism and detoxication effects of Artemisinin B in combination with DDP, the studies will be carried out as follows: (1) Evaluating synergism and detoxication effects of Artemisinin B in combination with DDP; (2) Further investigating if the mechanism involves Cx, GJ and other target proteins; (3) Exploring the signaling pathways involved in the regulation of GJ and Cx by Artemisinin B. The project aims to investigate the synergism and detoxication effects of Artemisinin B and to explore the underlying mechanism associate with Cx. The research findings can provide a scientific interpretation of the synergism and detoxication effects of Artemisinin B in combination with DDP, as well as the scientific information for the new application of artemisinins.
