Exploring The Mechanism Of Curcumol Against Breast Cancer Cell Metastasis Based On The Pentose Phosphate Pathway

Background and PurposeStudies have shown that among women suffering from cancer,the incidence and mortality of breast cancer rank first,and it is a major killer threatening women's lives and health.Among them,the important reason for the high mortality rate of breast cancer is metastasis.Traditional Chinese medicine theory believes that tumor is a kind of accumulation,caused by poor qi stagnation,blood stasis and stagnation.Therefore,in the anti-tumor treatment of traditional Chinese medicine,promoting blood circulation and removing blood stasis is an important treatment.Among the drugs for promoting blood circulation and removing blood stasis,it is the hemolytic drug with the strongest effect,and it is often used to treat gynecological diseases.Tumor cells use aerobic glycolysis as their metabolic feature.This metabolic method provides rapid energy for the growth,proliferation and maintenance of tumor cells.Since lactic acid,the final product of aerobic glycolysis,can lower the pH of the tumor tissue microenvironment,and the acidic tumor microenvironment will trigger the migration and invasion of tumor cells,so the tumor cells will acquire different metabolic characteristics in their metastatic pathways,Including the increase in the activity of its branched pathway pentose phosphate pathway(PPP),provides a material basis for the rapid proliferation of tumor cells.In the dialectics of traditional Chinese medicine,the energy metabolism of hyperplastic tissue is also aerobic glycolysis,which is similar to tumor tissue.Therefore,this suggests that when hemostatic drugs eliminate stasis and clumps,they can also have an impact on the energy metabolism at the site of action.Curcumol is one of the main ingredients of the curative drug Curcuma.Research has shown that it can play an anti-tumor effect by blocking the tumor cell cycle,inducing tumor cell apoptosis and differentiation,and inhibiting tumor cell nuclear metabolism.In this study,curcumol was used as the object,on the basis of verifying its anti-breast cancer high metastasis cell MDA-MB-231 metastasis,the pentose phosphate metabolic pathway was combined with metastasis to explore curcumol on MDA-MB-231 pentose phosphate The influence of the pathway and clarify the molecular mechanism of its specific role provide a theoretical basis for the research of anti-tumor metastasis of expelling blood circulation drug.Research Contents and ResultsIn this study,scratches.Transwell,and MDA-MB-231 lung conversion models were used to investigate the effect of curcumol on breast cancer metastasis.The results showed that curcumol can effectively inhibit the in vivo and in vitro metastasis of MDA-MB-231.Using kits,Western Blot and qPCR tests,curcumol can effectively inhibit HK2 expression,lactic acid production,G6PDH activity and its catalytic product NADPH production in MDA-MB-231 cells.Through flow cytometry and kit testing,it was further found that curcumol can increase the intracellular ROS level by inhibiting the production of NADPH,and also inhibit the production of GSH,reducing the oxidative stress capacity of MDA-MB-231 cells.Through immunofluorescence,Western Blot,and immunohistochemistry experiments,it was found that curcumol can inhibit the nucleation of the key kinase G6PDH of the pentose phosphate pathway,thereby inhibiting the production of its subsequent catalytic products to achieve the effect of inhibiting the pentose phosphate pathway.This is done by suppressing the expression of importin 13.Conclusion and SignificanceThis study starts from the hemolytic drug-component-target,and links the efficacy of the hemolytic drug Huayu Sanjie with energy metabolism,looking for a new perspective to reveal the common mechanism of anti-tumor metastasis of hemolytic drugs,and the effective activity of turmeric The component,curcumol,was used to conduct experiments to lay an experimental foundation for studying the antitumor metastasis effect of hemolytic drugs,and also to provide theoretical support for solving the doubts about clinical use of hemolytic drugs for tumors.This project confirmed the effect of curcumol on breast cancer cell MDA-MB-231 metastasis through in vivo and in vitro experiments,and found that the effect depends on the activity of G6PDH.Curcumol reduces the activity of G6PDH,reduces the expression of NADPH,TKT,GSH,and inhibits the production of lactic acid.By regulating importin 13,it inhibits the nucleus of G6PDH.