Multidrug resistance protein 5 affects cell proliferation, migration and gemcitabine sensitivity in pancreatic cancer MIA Paca‑2 and PANC‑1 cells

He,Ji; Bugde,Piyush; Li,Jiawei; Biswas,Riya; Li,Siting; Yang,Xuewei; Tian,Fang; Wu,Zimei; Li,Yan

doi:10.3892/or.2023.8666

Multidrug resistance protein 5 affects cell proliferation, migration and gemcitabine sensitivity in pancreatic cancer MIA Paca‑2 and PANC‑1 cells

Authors:
- Ji He
- Piyush Bugde
- Jiawei Li
- Riya Biswas
- Siting Li
- Xuewei Yang
- Fang Tian
- Zimei Wu
- Yan Li
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Affiliations: Department of Biomedicine and Medical Diagnostics, School of Science, Auckland University of Technology, Auckland 1010, New Zealand, Guangdong Key Laboratory of Plant Epigenetics, College of Life Sciences and Oceanography, Shenzhen University, Shenzhen 518060, P.R. China, Nycrist Pharmatech Limited, Shenzhen 518107, P.R. China, School of Pharmacy, Faculty of Medical and Health Sciences, University of Auckland, Auckland 1023, New Zealand
Published online on: November 16, 2023 https://doi.org/10.3892/or.2023.8666
Article Number: 7
Copyright: © He et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Gemcitabine‑based chemotherapy has been widely adopted as the standard and preferred chemotherapy regimen for treating advanced pancreatic cancer. However, the contribution of multidrug resistance protein 5 (MRP5) to gemcitabine resistance and pancreatic cancer progression remains controversial. In the present study, the effect of silencing MRP5 on gemcitabine resistance and cell proliferation and migration of human pancreatic cancer MIA Paca‑2 and PANC‑1 cells was investigated by using short‑hairpin RNA delivered by lentiviral vector transduction. The knockdown of MRP5 was confirmed on both mRNA and protein levels using qPCR and surface staining assays, respectively. MRP5‑regulated gemcitabine sensitivity was assessed by MTT, PrestoBlue and apoptosis assays. The effect of MRP5 on pancreatic cancer cell proliferation and migration was determined using colony‑formation, wound‑healing and Transwell migration assays. The interaction of gemcitabine and cyclic guanosine monophosphate (cGMP) with MRP5 protein was explored using molecular docking. The results indicated that the MRP5 mRNA and protein levels were significantly reduced in all the MIA Paca‑2 and PANC‑1 clones. MRP5 affected gemcitabine cytotoxicity and the rate of gemcitabine‑induced apoptosis. Silencing MRP5 decreased cell proliferation and migration in both MIA Paca‑2 and PANC‑1 cells. Docking studies showed high binding affinity of cGMP towards MRP5, indicating the potential of MRP5‑mediated cGMP accumulation in the microenvironment. In conclusion, MRP5 has an important role in cancer proliferation and migration in addition to its drug efflux functions in two widely available pancreatic tumour cell lines (MIA Paca‑2 and PANC‑1).

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