Guggulsterone Enhanced Inhibitory Effect Of Temozolomide On Glioblastoma Cells Through EGFR/PI3K/AKT/NF-κB Dependent Pathway

Objective: To investigate the effect and mechanism of the combination of Zguggulsterone and temozolomide in inhibiting human glioblastoma U87 cells.Methods: Glioblastoma U87 cells were treated with Z-guggulsterone and temozolomide alone or in combination.In vitro,cell proliferation was determined by CCK-8,the level of apoptosis was evaluated by flow cytometry,EGFR/PI3K/AKT/NF-κB pathway activity and the level of apoptosis-associated proteins Bcl-2 and BAX expression in the cells were analysed by Western blot.In vivo,a model of U87 subcutaneous transplantation in nude mice was established to observe the effects of Z-guggulsterone and temozolomide alone and in combination on tumor growth.The cell morphology in the tumors was observed by HE staining.PCNA and Ki-67 expression in the tumors were detected by immunohistochemistry.EGFR/PI3K/AKT/NF-κB pathway activity and the level of apoptosis-associated proteins Bcl-2 and BAX expression in the tumors were analysed by Western blot.Results: In vitro,Z-guggulsterone(100μM)significantly enhanced the antiproliferation and pro-apoptosis effect of temozolomide on U87 cells,as compared with temozolomide treatment alone.Z-Gguggulsterone(100μM)significantly downregulated the expression of EGFR、p-EGFR、PI3K p110、PI3K p85、IKK-α、IκB-α、p-IκB-α、p-NF-κB/p65 and Bcl-2,as compared with temozolomide treatment alone.In vivo,Z-guggulsterone(30mg/kg)significantly reduced the final tumor volume,as compared with temozolomide(3mg/kg)treatment alone.ZGuggulsterone(30mg/kg)significantly down-regulated the expression of PCNA、Ki-67、EGFR、PI3K p110 and p-NF-κB/p65,as compared with temozolomide(3mg/kg)treatment alone.Conclusion: Z-Guggulsterone enhances the inhibitory effect of temozolomide on human glioblastoma U87 cells through EGFR/PI3K/AKT/NF-κB dependent pathway in vitro and vivo.