Does Multidrug Resistance Protein 5 (MRP5) Contribute to Acquired Resistance to Gemcitabine in the Human Pancreatic Cancer PANC-1 Cell Line?

Morathoti, Simmi Rao
Li, Yan
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Master of Science
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Auckland University of Technology

Objectives: Pancreatic cancer is among the largest cause of cancer-related deaths in New Zealand with a grim prognosis of approximately 3-5 months if left untreated. The present research aimed to generate gemcitabine resistant PANC-1 cell lines, determine sensitivities, and investigate changes in the expression of a key ABC transporter (ABCC5).

Method: PANC-1 cell cultures were grown and split in preparation for gemcitabine treatment. Increasing concentrations of gemcitabine (20 nM, 100 nM, 200 nM, 2000 nM, 4000 nM) were added to respective vials of PANC-1 cells to determine growth and cell viability was calculated. Using GAPDH as an internal control, the relative gene expression of ABCC5 was analysed by using quantitative real-time PCR (qRT-PCR).

Results: PANC-1 cell viability increased as gemcitabine concentrations increased showing that PANC-1 cells gained resistance to treatment. Additionally, post-qRT-PCR analysis, a fold change of 1065 was determined for the expression of the ABCC5 gene suggesting a statistically significant increase in the upregulation of ABCC5 mRNA transcripts in PANC-1 cells treated with increased gemcitabine concentrations.

Conclusions: Accordingly, it seems that gemcitabine treatment induced its resistance in a commonly used pancreatic cell line by upregulating the expression of proteins that aid in the efflux of anti-cancer medication. These results shed some light on the unknowns of chemotherapy drug effectiveness and may explain a cause for common chemotherapy medication resistance.

PANC-1, Pancreatic cancer, ABCC5, MRP5
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