Abstract A041: Gene expression alteration in chronic hypoxic PANC-1 pancreatic cancer cell line

Abstract

Abstract Background: Cancer cells grow uncontrollably by disregarding the normal rule of cell division; the resulting overcrowding of cancer cells leads to a decrease in oxygen availability, which is known as hypoxia. The role of tumor hypoxia has become a main focus in cancer research since it is a driving force in promoting tumor progression, malignancy, and resistance to therapy. Hypoxia is a prominent feature of the tumor microenvironment of pancreatic tumors. Objective: The main purpose of this study was to identify the changes in gene expression associated with chronic hypoxia in PANC-1 pancreatic cancer cell line. Methodology: Pancreatic cancer cells (PANC-1) were exposed to 8-hour hypoxic episodes (<1% oxygen) three times a week for a total of 40 episodes. The alterations in gene expression were examined using the real-time based PCR array technology after 20 and 40 episodes of hypoxia and compared to normoxic cells. Chemo-resistance of hypoxic cells toward doxorubicin was assessed using MTT cell proliferation assay. Cell migration was evaluated using wound healing assay. Results: Noticeable gene expression changes were identified after 20 and 40 episodes of hypoxia. No changes were common in both stages, with most genes rebounding at the level of 40 episodes. Notably, genes HIF1AN, HMOX-1, and PKM have been remarkably upregulated by 6.9, 4.5, and 3.4 fold, respectively, after 20 hypoxic shots. The half-maximal inhibitory concentration (IC50) of doxorubicin in PANC-1 cells has increased by approximately 2.7 fold after 20 episodes of hypoxia and increased by approximately 3.6 fold after 40 episodes compared to normoxic cells. Conclusion: This study provided evidence that exposing cells to prolonged periods of hypoxia (weeks) results in different expression changes than those induced by short-term hypoxia (<72 hours). It also approved induction of chemo-resistance by chronic hypoxia. Finally, it proposed HIF1AN, HMOX-1, and PKM as a potential biomarkers for hypoxia in pancreatic cancer and as main players in the cellular response to chronic hypoxia. Citation Format: Malek A. Zihlif, Layaly Hisham Younis Hisham Younis, Ahmad Sharab Sharab. Gene expression alteration in chronic hypoxic PANC-1 pancreatic cancer cell line [abstract]. In: Proceedings of the AACR-NCI-EORTC International Conference: Molecular Targets and Cancer Therapeutics; 2017 Oct 26-30; Philadelphia, PA. Philadelphia (PA): AACR; Mol Cancer Ther 2018;17(1 Suppl):Abstract nr A041.