J Cancer 2020; 11(3):657-667. doi:10.7150/jca.38350

Research Paper

Bazedoxifene enhances paclitaxel efficacy to suppress glioblastoma via altering Hippo/YAP pathway

Weiwei Fu1*, Peng Zhao1*, Hong Li1, Haiyang Fu1, Xuejun Liu2, Yingchao Liu3, Jie Wu3, Weiwei Fu1✉

1. Department of Pathology, The Affiliated Hospital of Qingdao University, Qingdao, Shandong 266003, P. R. China;
2. Department of Radiology, The Affiliated Hospital of Qingdao University, Qingdao, Shandong 266003, P. R. China;
3. Department of Neurosurgery, Provincial Hospital Affiliated to Shandong University, Jinan, Shandong 250006, P. R. China.
*Contributed equally

This is an open access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/). See http://ivyspring.com/terms for full terms and conditions.
Citation:
Fu W, Zhao P, Li H, Fu H, Liu X, Liu Y, Wu J, Fu W. Bazedoxifene enhances paclitaxel efficacy to suppress glioblastoma via altering Hippo/YAP pathway. J Cancer 2020; 11(3):657-667. doi:10.7150/jca.38350. Available from http://www.jcancer.org/v11p0657.htm

File import instruction

Abstract

Glioblastoma multiform (GBM) is an aggressive type of brain tumor originated from astrocytes. Owing to the limited therapeutic options, intensive efforts are still being made to find novel treatments for GBM. In this study, we first identified that bazedoxifene bore the ability to reduce cell survival and cell invasion of glioblastoma cells. Furthermore, our results also revealed that bazedoxifene combining with paclitaxel had better efficacy to suppress glioblastoma progression by promoting apoptosis and reducing EMT. Combination of bazedoxifene and paclitaxel also accelerated YAP phosphorylation and inactivation. Importantly, preclinical animal model also verified our in vitro findings. Together, our data not only define the underlying mechanism responsible for action of bazedoxifene on glioblastoma cells but also build strong rational to develop bazedoxifene for the treatment of GBM patients.

Keywords: Bazedoxifene, Paclitaxel, Glioblastoma, YAP