基于“热证-代谢”穿越体探讨清热解毒法调控乳腺癌Warburg效应的作用机制

Detoxification is an important treatment of cancer in Traditional Chinese Medicine,which antitumor mechanism is the hot spot in recent years. Under the guidance of "heat syndrome-metabolism", the research group has conducted a preliminary study on the anti-tumor mechanism of heat clearing and detoxicating method: The detoxification method could inhibit the growth and proliferation of breast cancer cells by interventing the glucose metabolism of cancer cells, but the specific mechanism of detoxicating in regulation Warburg effect (aerobic glycolysis) of breast cancer cell was unclear..High expression of manganese superoxide dismutase (MnSOD) is the key step to inhibit Warburg effect of tumor cells, at the same time,our previous studies confirmed that the detoxification method could significantly improve the content and activity of serum SOD in nude mice model of breast cancer, therefore,this project wants to investigate whether detoxification method regulates the Warburg mechanism of MCF-7 breast cancer cells by inducing high expression of MnSOD in vitro and in vivo experiments, which uses human breast cancer cell lines、primary breast cancer cells and transplanted nude mice model, the main object of this project is to explain the mechanism of detoxification method against breast cancer and explore the specific target of Warburg effect for traditional Chinese medicine in treatment of breast cancer, and the experimental basis is provided in tumor metabolism research and therapeutic areas by detoxification method.

清热解毒是中医治疗肿瘤的重要治法，针对其抗肿瘤作用机制的研究是近年来的热点。在“热证-代谢”穿越体的启发下，课题组也对清热解毒法的抗肿瘤机制进行了前期研究：结果发现清热解毒法能够通过干预乳腺癌糖代谢途径从而抑制乳腺癌细胞的生长和增殖，但清热解毒法调控乳腺癌细胞warburg效应（有氧糖酵解）的具体机制尚不明确。.锰超氧化物歧化酶（MnSOD）高表达是抑制肿瘤细胞warburg效应的关键环节，结合课题组既往研究证实清热解毒法能显著提高乳腺癌裸鼠模型血清中SOD的含量和活性，因此本项目拟通过体外、体内实验，利用人乳腺癌细胞株和原代乳腺癌细胞、建立移植性裸鼠模型，探讨清热解毒法是否通过诱导MnSOD高表达从而调控乳腺癌MCF-7细胞warburg效应，以阐释清热解毒法抗乳腺癌的作用机制，明确清热解毒中药干预乳腺癌warburg效应的作用靶点，并为清热解毒法在肿瘤代谢领域的研究和应用提供实验依据。