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:[email protected]
Jian Yang, email:[email protected]
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.
