中文摘要
破血药临床抗肿瘤应用广,但对肿瘤转移是促进还是抑制争论不一。本项目拟结合Warburg效应的有氧糖酵解理论(肿瘤细胞的特征性能量代谢方式)揭示破血药化瘀散结对肿瘤转移的影响及其分子机制。首先,中医认为肿瘤属于典型的血瘀证,治以化瘀散结。则破血药化瘀散结去肿瘤血瘀的实质应是干扰肿瘤组织的有氧糖酵解能量代谢模式,破坏其特定微环境;其次,越来越多的数据证实,破血药对有氧糖酵解促进肿瘤转移的关键环节血管生成有抑制作用;最后,干扰肿瘤能量代谢符合中医治本的治病原则。因此认为:破血药抑制肿瘤转移,其分子机制与有氧糖酵解能量代谢及调控过程有关。研究内容:探究破血药影响己糖激酶、6磷酸果糖激酶或丙酮酸激酶等糖代谢限速酶介导的有氧糖酵解能量代谢及调控过程,及其与肿瘤细胞粘附、运动和迁移之间的关系。意义:明确破血药抑制肿瘤转移及其分子机制,消除临床使用疑虑;确定有抑制肿瘤转移作用并有新药创制前景的效应成分。
英文摘要
POXUE herbs were used widely in clinic for treatment of cancer. However, it is unconfirmed whether it inhibits tumor metastasis or facilitates it. The project is to elucidate how poxue herbs affect tumor metastasis based on Warburg effect and its molecular mechanism. Firstly, the traditional theory regards the solid tumor as the severe blood stasis syndrome which is relieved by removing the blood stasis and dissolving the microvessels. So the intrinsic mechanism that poxue herbs remove the stasis in tumor issue is to disturb the way of energy metabolism----- Aerobic glycolysis, breaking the specified circumstance for tumor growth and metastasis. Secondly, cumulative data justified that angiogenesis mediating the aerobic glycolysis and tumor metastasis was inhibited by poxue herbs. Finally, inhibition of aerobic glycolysis is consistent with the macroscopic therapeutic theory of traditional medicine. Thus, it is concluded that the poxue herbs inhibit tumor metastasis and its molecular mechanism is related to the course of aerobic glycolysis. The project is to find out how poxue herbs affect the rate-limiting enzyme (HK, PFK, PKM)-mediated the course of aerobic glycolysis, resulting in the alteration of adhension, motility and migration in cancer cells. Research significance: confirm the inhibitory effect of poxue herbs on tumor metastasis and its molecular mechanism to help the physician use poxue herbs correctly, and find the prospective active compounds for inhibition of metastasis.
