Genes & Cancer

Key drug-targeting genes in pancreatic ductal adenocarcinoma

Meena Kishore Sakharkar1, Sarinder Kaur Dhillon2, Mohit Mazumder3, Jian Yang1

1Drug Discovery and Development Research Group, College of Pharmacy and Nutrition, University of Saskatchewan, Saskatoon, SK, Canada

2 Institute of Biological Sciences, Faculty of Science, University of Malaya, Kuala Lumpur, Malaysia

3 School of Life Sciences, Jawaharlal Nehru University, New Delhi, India

Correspondence:

Meena Kishore Sakharkar, email:meena.sakharkar@usask.ca


Jian Yang, email:jian.yang@usask.ca

Keywords: pancreatic ductal adenocarcinoma; differentially expressed genes; protein-protein interaction network (PPI); fibronectin 1; serpin peptidase inhibitor B5

Received: November 11, 2020 Accepted: January 21, 2021 Published: March 11, 2021

Abstract

Pancreatic ductal adenocarcinoma (PDAC) is a highly lethal type of cancer. In this study, we undertook a pairwise comparison of gene expression pattern between tumor tissue and its matching adjacent normal tissue for 45 PDAC patients and identified 22 upregulated and 32 downregulated genes. PPI network revealed that fibronectin 1 and serpin peptidase inhibitor B5 were the most interconnected upregulated-nodes. Virtual screening identified bleomycin exhibited reasonably strong binding to both proteins. Effect of bleomycin on cell viability was examined against two PDAC cell lines, AsPC-1 and MIA PaCa-2. AsPC-1 did not respond to bleomycin, however, MIA PaCa-2 responded to bleomycin with an IC50 of 2.6 μM. This implicates that bleomycin could be repurposed for the treatment of PDAC, especially in combination with other chemotherapy agents. In vivo mouse xenograft studies and patient clinical trials are warranted to understand the functional mechanism of bleomycin towards PDAC and optimize its therapeutic efficacy. Furthermore, we will evaluate the antitumor activity of the other identified drugs in our future studies.


PII: 210