Marsdenia tenacissima injection induces the apoptosis of prostate cancer by regulating the AKT/GSK3β/STAT3 signaling axis  

作　　者：LI Xiaolan HE Songhua LIANG Wei ZHANG Weiquan CHEN Xin LI Qiaofeng YANG Xin LIU Yanying ZHU Dan LI Li LIU Buming SU Zhiheng CHEN Jie GUO Hongwei 

机构地区：[1]Guangxi Key Laboratory of Bioactive Molecules Research and Evaluation&College of Pharmacy,Guangxi Medical University,Nanning 530021,China [2]Key Laboratory of Longevity and Aging-related Diseases of Chinese Ministry of Education&Center for Translational Medicine,Guangxi Medical University,Nanning 530021,China [3]Guangxi Institute for Food and Drug Control,Drug Administration of Zhuang Autonomous Region,Nanning 530021,China [4]Guangxi Key Laboratory of Traditional Chinese Medicine Quality Standards,Guangxi Institute of Chinese Medicine&Pharmaceutical Science,Nanning 530022,China [5]The Affiliated Tumor Hospital,Guangxi Medical University,Nanning 530021,China

出　　处：《Chinese Journal of Natural Medicines》2023年第2期113-126,共14页中国天然药物（英文版）

基　　金：supported by the National Natural Science Foundation of China(No.82160948);Guangxi Natural Science Foundation(No.2022JJD140152);the Open Project of Guangxi Key Laboratory of Traditional Chinese Medicine Quality Standards(No.GUIZHONGZHONGKAI 202004)。

摘　　要：Marsdenia tenacissima injection,a standard Marsdenia tenacissima extract(MTE),has been approved as an adjuvant therapeutic agent for various cancers.Our previous study showed that MTE inhibited the proliferation and metastasis of prostate cancer(PCa)cells.However,the underlying mechanisms and active ingredients of MTE against PCa were not completely understood.This study revealed that MTE induced significant decreases in cell viability and clonal growth in PCa cells.In addition,MTE induced the apoptosis of DU145 cells by reducing the mitochondrial membrane potential and increasing the expression of Cleaved Caspase 3/7,Cyt c,and Bax.In vivo,DU145 xenografted NOD-SCID mice treated with MTE showed significantly decreased tumor size.TUNEL staining and Western blot confirmed the pro-apoptotic effects of MTE.Network pharmacology analysis collected 196 ingredients of MTE linked to 655 potential targets,and 709 PCa-associated targets were retrieved,from which 149 overlapped targets were screened out.Pathway enrichment analysis showed that the HIF-1,PI3K-AKT,and ErbB signaling pathways were closely related to tumor apoptosis.Western blot results confirmed that MTE increased the expression of p-AKT^(Ser473) and p-GSK3β^(Ser9),and decreased the expression of p-STAT3^(Tyr705) in vitro and in vivo.A total of 13 compounds in MTE were identified by HPLC-CAD-QTOF-MS/MS and UPLCQTOF-MS/MS.Molecular docking analysis indicated that six compounds may interact with AKT,GSK3β,and STAT3.In conclusion,MTE induces the endogenous mitochondrial apoptosis of PCa by regulating the AKT/GSK3β/STAT3 signaling axis,resulting in inhibition of PCa growth in vitro and in vivo.

关 键 词：Marsdenia tenacissima injection Prostate cancer APOPTOSIS AKT/GSK3β/STAT3 

分 类 号：R965[医药卫生—药理学]