摘要
目的研究醉茄素A(withaferin,WA)联合顺铂(cisplatin,DDP)对宫颈癌的协同作用及机制。方法以宫颈癌细胞系为对象,采用MTT法检测WA对DDP的协同增效作用。通过Annexin V-FITC/PI染色法、TUNEL法和Western blot法探究WA联合DDP对宫颈癌细胞凋亡的诱导作用。使用免疫荧光法和免疫印迹法检测NF-κB/MDR1通路相关蛋白。细胞内的活性氧(reactive oxygen species,ROS)水平通过DCFH-DA和MitoSOX法进行测定。采用裸鼠移植瘤模型在动物水平上评价WA对DDP的增效作用。结果WA与DDP联合用药可协同抑制宫颈癌细胞存活,促进细胞凋亡,并对荷瘤小鼠的肿瘤有明显的生长抑制作用。WA能抑制DDP诱导的NF-κB/MDR1信号通路的激活,并促进ROS的产生。结论WA通过抑制DDP诱导的NF-κB/MDR1通路激活和增强DDP诱导的ROS产生,发挥抗宫颈癌协同增效作用。
Aim To study the synergistic effect of withaferin A(WA)combined with cisplatin(DDP)on cervical cancer and its mechanism.Methods MTT assay was employed to detect the synergistic effect of WA on DDP in cervical cancer cell lines.Annexin V-FITC/PI staining,TUNEL assay and immunoblotting were used to investigate the effect of WA combined with DDP on apoptosis of cervical cancer cells.Immunofluorescence and immunoblotting were used to detect NF-κB/MDR1 pathway related proteins.DCFH-DA and MitoSOX were applied to determine the intracellular reactive oxygen species(ROS)levels.A xenograft model was also used to evaluate the synergistic effect of WA on DDP.Results The combination of WA and DDP could inhibit the survival of cervical cancer cells,promote apoptosis,and inhibit the growth of tumor in mice.WA could inhibit DDP-induced NF-κB/MDR1 signaling pathway and promote ROS production.Conclusions WA plays a synergistic role in anti-cervical cancer by inhibiting DDP-induced NF-κB/MDR1 pathway activation and enhancing DDP induced ROS production.
作者
李威
石忠秀
黄勇
程志颖
董嘉慧
龙青青
何杉
刘涛
王呈呈
LI Wei;SHI Zhong-xiu;HUANG Yong;CHENG Zhi-ying;DONG Jia-hui;LONG Qing-qing;HE Shan;LIU Tao;WANG Cheng-cheng(Bijie Market Supervision Administration Inspection and Testing Center,Bijie,Guizhou 551700,China;School of Medicine,Guizhou University,Guiyang 550025,China)
出处
《中国药理学通报》
CAS
CSCD
北大核心
2023年第6期1127-1135,共9页
Chinese Pharmacological Bulletin
基金
国家自然科学基金资助项目(No 31960179)
贵州省科技基金资助项目(No黔科合基础[2020]1Y086)
贵州省卫生健康委员会科技基金项目(No gzwkj2022-219)
贵州省研究生科研基金项目(No黔教合YJSCXJH﹝2020﹞186)。
