Survivin Promotes Piperlongumine Resistance in Ovarian Cancer

Frontiers in Oncology

Xiao-Jian Yan¹  Hai-Hong Zhou²  Xing-Wei Nan²  Piao-Piao Ye²  Li-Hua Gong²  Xu Chen²  Kun Liu³  Zi-Hao Xing³  Yang Yang³  Zhi Shi³  Sheng-Te Wang³  Meng-Ning Wei³  Yao Li³ 

[1] Center for Uterine Cancer Diagnosis &Department of Gynecology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China;Guangdong Provincial Key Laboratory of Bioengineering Medicine, Department of Cell Biology and Institute of Biomedicine, National Engineering Research Center of Genetic Medicine, College of Life Science and Technology, Jinan University, Guangzhou, China;

关键词: piperlongumine;    survivin;    ovarian cancer;    ROS;    proteasome;   

DOI  :  10.3389/fonc.2019.01345

来源: DOAJ

【 摘 要 】

Ovarian cancer is one of the most fatal female malignancies while targeting apoptosis is critical for improving ovarian cancer patients' lives. Survivin is regarded as the most robust anti-apoptosis protein, and its overexpression in ovarian cancer is related to poor survival and apoptosis resistance. Piperlongumine (PL) extracted from peppers is defined as an active alkaloid/amide and exhibits a broad spectrum of antitumor effects. Here, we demonstrate that PL induces the rapid depletion of survivin protein levels via reactive oxygen species (ROS)-mediated proteasome-dependent pathway in vitro, while exerting a remarkable inhibitory influence on the proliferation of ovarian cancer cells. Overexpression of survivin raises the survival rate of ovarian cancer cells to PL. Moreover, PL inhibits ovarian cancer cells xenograft tumor growth and downregulates survivin in vivo. Our findings reveal a previously unrecognized mechanism of PL in suppressing survivin expression as well as survivin promotes piperlongumine resistance in ovarian cancer and suggest that ROS-mediated proteasome-dependent pathway can be exploited to overcome apoptosis resistance triggered by aberrant expression of survivin.

【 授权许可】

Unknown