The gene expression alterations in chronic hypoxic PANC-1 pancreatic cancer cell line

Pharmacy Practice

  • Malek Zihlif1Department of Pharmacology, School of Medicine, The University of Jordan, Amman 11942, Jordan.
  • Heba A Khader2Department of Clinical Pharmacy and Pharmacy Practice, Faculty of Pharmaceutical Sciences, The Hashemite University, Zarqa, Jordan.
  • Layali Younis1Department of Pharmacology, School of Medicine, The University of Jordan, Amman 11942, Jordan.
  • Ahmad Sharab1Department of Pharmacology, School of Medicine, The University of Jordan, Amman 11942, Jordan.
  • Farah Tahboub1Department of Pharmacology, School of Medicine, The University of Jordan, Amman 11942, Jordan.
  • Luai Hasoun3Department of Clinical Pharmacy and Therapeutics, Faculty of Pharmacy, Applied Science Private University (ASU), Amman, Jordan.
  • Hamzah Hajaj4Department of Pathology, Microbiology, and Forensic Medicine, School of Medicine, The University of Jordan, Jordan.
  • Zaid Alawneh4Department of Pathology, Microbiology, and Forensic Medicine, School of Medicine, The University of Jordan, Jordan.
  • Ahmad R. Alsayed3Department of Clinical Pharmacy and Therapeutics, Faculty of Pharmacy, Applied Science Private University (ASU), Amman, Jordan.

Volume 23 Issue 4 Pages 1-8

DOI: 10.18549/PharmPract.2025.4.3238

Abstract

Aim: Cancer cells divide excessively, resulting in overpopulation and hypoxia. Tumor hypoxia drives tumor development and therapeutic resistance. Hypoxia dominates pancreatic tumor microenvironments. This study aimed to ascertain alterations in gene expression linked to chronic hypoxia in the pancreatic cancer cell (PANC-1) line. Methods: PANC-1 had eight-hour hypoxic events with oxygen levels below 1%. 40 episodes were exposed three times a week. Real-time PCR arrays were used to analyze gene expression changes. This investigation compared cells treated with 20 and 40 hypoxia episodes to normoxic cells. MTT cell proliferation assays assessed hypoxic cell doxorubicin resistance. Wound-healing assays measured cell migration. 20 and 40 hypoxia exposures altered gene expression patterns significantly. Results: No alterations were observed in either stage, as most genes exhibited a resurgence after 40 episodes. Following exposure to 20 episodes of hypoxia, the expression levels of the genes HIF1AN, HMOX-1, and PKM were significantly increased by factors of 6.9, 4.5, and 3.4, respectively. The IC50 value of Doxorubicin in PANC-1 cells exhibited a 2.7-fold increase and an approximately 3.6-fold increase after 20 and 40 episodes, respectively, compared to normoxic cells. This study demonstrates that subjecting cells to extended durations of hypoxia results in distinct alterations in gene expression compared to those induced by short-term hypoxia, specifically lasting less than 72 hours. Furthermore, it sanctioned the facilitation of chemotherapy resistance through prolonged exposure. Conclusions: The study suggests that HIF1AN, HMOX-1, and PKM may serve as promising biomarkers for hypoxia in pancreatic cancer and contributors to the cellular response to prolonged hypoxia.

Keywords

  • Cancer
  • Cell Line
  • Gene Expression
  • Hyoxia
  • PANC-1
Pharmacy Practice

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