Synergistic inhibition effect of hydroxychloroquine and bevacizumab on HUVEC cell growth and its mechanism
10.3969/j.issn.1001-1978.2019.11.018
- Author:
Zixue XUAN
1
Author Information
1. Dept of Pharmacy, Zhejiang Provincial People's Hospital, People's Hospital of Hangzhou Medical College
- Publication Type:Journal Article
- Keywords:
autophagy;
bevacizumab;
differentially expressed genes;
HUV E C;
hydroxychloroquine;
RNA-seq
- From:
Chinese Pharmacological Bulletin
2019;35(11):1575-1582
- CountryChina
- Language:Chinese
-
Abstract:
; Aim To study the synergistic inhibition effect of hydroxychloroquine (HCQ) and bevacizumab (B E V) on the cell growth of HUVECs and its mechanism. Methods RTCA,flow apoptosis assay and the vascularization assay of HUVECs were used to study the effect of HCQ combined with BEV on HUVEC proliferation, cell apoptosis and vascularization. The expressions of LC3 and p62 proteins were detected by Western blot, autophagy flow was observed through m Cherry EGFPLC3 double fluorescence, the changes of autophagosome and mitochondria were observed by electron microscopy, and the regulatory molecular mechanism of HCQ combined with BEV was revealed by transcriptome sequencing (RNA-seq). Results Compared with single drug groups, the combination of HCQ and BEV could synergistically inhibit HUVEC proliferation, promote HUVEC apoptosis, and inhibit the formation of vascular structures in HUVECs. HCQ could inhibit autophagy of HUVECs. Transcriptome sequencing results showed that the combination of HCQ and BEV influenced 69 different expressed genes,and the combination of HCQ and BEV might synergistically inhibit HUVECs by regulating "hub" genes such as RICTOR and PIK3CA. Conclusions The combination of HCQ and BEV can synergistically inhibit HUVECs, which is related to not only the inhibition of autophagy by HCQ, but also the regulation of " hub " genes such as RICTOR and PIK3CA.
