Liuyun Gong1, Yutiantian Lei1, Xinyue Tan1, Yiping Dong1, Zhenzhen Luo1, Dan Zhang2, Suxia Han3. 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.
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.
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.
Authors: Marian Cruz-Burgos; Alberto Losada-Garcia; Carlos D Cruz-Hernández; Sergio A Cortés-Ramírez; Ignacio Camacho-Arroyo; Vanessa Gonzalez-Covarrubias; Miguel Morales-Pacheco; Samantha I Trujillo-Bornios; Mauricio Rodríguez-Dorantes Journal: Front Oncol Date: 2021-02-26 Impact factor: 6.244