The Research And Mechanism Of Zhenqi Fuzheng Capsule Combined With Temozolomide Against Glioma Cell Resistance

Purpose: Glioblastoma(GBM)is the most common aggressive malignant tumor in the brain.At present,the treatment of glioma mainly includes surgery,radiotherapy and chemotherapy.Temozolomide(TMZ)is an effective oral chemotherapy drug for glioma.TMZ resistance is still one of the main reasons for the failure of glioma treatment.The combination of traditional Chinese medicine and Western medicine has been proved to change the resistance of tumors to Western medicine,and it is one of the treatment methods to solve the resistance of tumors.Zhenqi Fuzheng Capsule is one of the commonly used traditional Chinese medicine preparations in clinic.Studies have shown that Zhenqi Fuzheng Capsule has certain clinical efficacy in the treatment of various cancers,but Zhenqi Fuzheng Capsule has not been used in the treatment of glioma.In this paper,we studied and compared the effects of Zhenqi Fuzheng Capsule,TMZ and Zhenqi Fuzheng Capsule combined with TMZ on the cell viability and apoptosis of glioma TMZ-resistant U87 cell line,and preliminarily discussed the molecular mechanism of the effect of Hezhenqi Fuzheng Capsule on glioma TMZ-resistant U87 cell line.Material and method:TMZ-resistant cell line U87/TMZ was induced by increasing TMZ concentration gradually.U87/TMZ was treated with 50ug/mL Zhenqi Fuzheng capsule,300 mM TMZ and 50ug/mL Zhenqi Fuzheng Capsule plus 300 mM TMZ alone.The expressions of AKT,AMPK and MTR in U87/TMZ were detected by Western blot,and then the expressions of PARP,cleaved caspase-3,autophagy-related LC3-II,pro-apoptotic were detected.The expression of protein Bax and anti-apoptosis proteins Bcl-2,the apoptosis of cells were detected by Annexin V,PI staining kit and flow cytometry,and the pharmacological activities of Zhenqi Fuzheng Capsule,TMZ,Zhenqi Fuzheng Capsule + TMZ on U87/TMZ were determined by MTT method.Results: 1.The combination of Zhenqi Fuzheng Capsule and TMZ can block AKT and MTR and activate AMPK?.2.The combination of Zhenqi Fuzheng Capsule and TMZ can increase cleaved PARP,cleaved caspase-3 and induce autophagy and apoptosis of U87/TMZ.3.The combination of Zhenqi Fuzheng Capsule and TMZ could induce 95% of U87/TMZ deaths,while the combination of Zhenqi Fuzheng Capsule and TMZ U87/TMZ alone had no significant effect.Conclusion: 1.Zhenqi Fuzheng Capsule can reverse the resistance of U87/TMZ to TMZ.2.The combination of Zhenqi Fuzheng Capsule and TMZ can block AKT/AMPK/MTOR signaling pathway and induce autophagy and apoptosis of U87/TMZ.3.The combination of Zhenqi Fuzheng Capsule and TMZ can also induce U87/TMZ death.