基于生物大数据库分析并验证附子去甲乌药碱抗肿瘤潜在作用机制

目的?以附子主要活性成分之一去甲乌药碱为代表，探究附子治疗肿瘤的作用及其可能的机制。方法?利用预测分析工具BATMAN-TCM及多种生物数据库预测去甲乌药碱调控肿瘤发生发展的可能机制；并通过体内外实验进行效应及机制的验证。结果?数据库分析显示，去甲乌药碱可能直接调控肿瘤细胞增殖、凋亡，或通过影响心脏功能而间接影响肿瘤发生发展；动物实验表明，去甲乌药碱可显著减小结肠癌皮下移植瘤的体积（P<0.05），促进瘤组织中肿瘤细胞的凋亡，并能显著提高结肠癌模型裸鼠体内心钠肽（ANP）水平（P<0.01），但细胞实验发现去甲乌药碱对肿瘤细胞无直接杀伤作用。结论?附子主要活性成分之一去甲乌药碱可抑制结肠癌皮下移植瘤的生长，诱导其凋亡，从而发挥抗肿瘤作用，其机制可能与促进心脏肽类激素ANP的释放有关，可为中医临床使用附子治疗恶性肿瘤提供一定的理论依据，但附子的毒性与抗肿瘤的关系还有待进一步研究。 

Analyze and Verify the Potential Anti-Tumor Mechanism of Higenamine in Aconitum Carmichaeli Debx<\i> Based on Biological Databases

OBJECTIVE?To explore the possible role and mechanism of Aconitum Carmichaeli Debx in the treatment of tumors， by using one of the main active components， higenamine as a representative. METHODS?BATMAN-TCM and various biological databases were used to predict the possible mechanism of higenamine in regulating the occurrence and development of tumor， and the effects and mechanisms were verified by in vivo and in vitro experiments. RESULTS?Database analysis showed that higenamine regulated the proliferation and apoptosis of tumor cells directly， or indirectly affected tumor occurrence and development by affecting heart function. The animal experiments showed that higenamine significantly reduced the volume of subcutaneous transplanted tumors of colon cancer (P<0.05)， promoted the apoptosis of tumor cells in tumor tissues， and significantly improved the secretion level of atrial natriuretic peptide (ANP) (P<0.01) of colon cancer model mice. However， the cell experiments found that higenamine had no direct killing effect on tumor cells. CONCLUSION?Higenamine， one of the main active components of Aconitum Carmichaeli Debx， can inhibit the growth of colon cancer subcutaneously transplanted tumors and induce tumor cells apoptosis， playing an anti-tumor effect. The mechanism may be related to the promotion of the release of cardiac peptide hormone ANP. It can provide a certain theoretical basis for the clinical use of Aconitum Carmichaeli Debx to treat malignant tumors. However， the relationship between the toxicity of Aconitum Carmichaeli Debx and its anti-tumor effect remains to be further studied.