Propranolol selectively inhibits cervical cancer cell growth by suppressing the cGMP/PKG pathway

Liuyun Gong; Yutiantian Lei; Xinyue Tan; Yiping Dong; Zhenzhen Luo; Dan Zhang; Suxia Han

doi:10.1016/j.biopha.2019.01.027

Propranolol selectively inhibits cervical cancer cell growth by suppressing the cGMP/PKG pathway

Biomed Pharmacother. 2019 Mar:111:1243-1248. doi: 10.1016/j.biopha.2019.01.027. Epub 2019 Jan 15.

Authors

Liuyun Gong¹, Yutiantian Lei¹, Xinyue Tan¹, Yiping Dong¹, Zhenzhen Luo¹, Dan Zhang², Suxia Han³

Affiliations

¹ Department of Oncology, The First Affiliated Hospital, Xi'an Jiaotong University, Xi'an, Shanxi, 710061, PR China.
² Department of Cell Biology and Genetics, School of Basic Medical Sciences, Xi'an Jiaotong University Health Science Center, Xi'an, Shanxi, 710061, PR China.
³ Department of Oncology, The First Affiliated Hospital, Xi'an Jiaotong University, Xi'an, Shanxi, 710061, PR China. Electronic address: shan87@mail.xjtu.edu.cn.

PMID: 30841438
DOI: 10.1016/j.biopha.2019.01.027

Abstract

Aim: To observe the effect of propranolol in cervical cancer and investigate the mechanism of the effect． METHODS AND RESULTS: We found 5 direct protein targets (DPTs) of propranolol (PRO) by DrugBank5.0 firstly. Next, we analyzed protein-protein interaction (PPI) network and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways of PRO DPTs and the result showed that PRO was linked with cGMP/PKG pathway. Then, we recognized the top 38 upexpressed genes of cervical cancer (CC) based original microarray datasets (GSE7803, GSE9750, GSE39001 and GSE63514). Further, we analyzed the biological process with the 38 overexpressed genes by STRING. We found some of overexpressed genes of CC participated in GMP biosynthetic process. Lastly, the function of PRO in CC was validated by MTT assay, Western blotting, flow cytometry and colony formation assay methods. We verified PRO can suppress cGMP/PKG pathway then inhibits CC cell growth.

Conclusion: The bioinformatical analysis combine with traditional experiment can help us understanding potential molecular mechanism about how PRO acting in CC. This method is a new paradigm which can guide future researches about mechanism in existing diseases and drugs.

Keywords: Apoptosis; Bioinformatical analysis; Cervical cancer; Proliferation; Propranolol; cGMP-PKG signaling pathway.

MeSH terms

Apoptosis / drug effects
Cell Line, Tumor
Cell Proliferation / drug effects*
Cyclic GMP / metabolism*
Cyclic GMP-Dependent Protein Kinases / metabolism*
Female
HeLa Cells
Humans
Propranolol / pharmacology*
Protein Interaction Maps / drug effects
Signal Transduction / drug effects*
Uterine Cervical Neoplasms / drug therapy*
Uterine Cervical Neoplasms / metabolism

Substances

Propranolol
Cyclic GMP-Dependent Protein Kinases
Cyclic GMP