Multidrug resistance protein 5 affects cell proliferation, migration and gemcitabine sensitivity in pancreatic cancer MIA Paca‑2 and PANC‑1 cells
- PMID: 37975256
- PMCID: PMC10696546
- 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
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).
Keywords: ABC transporters; MRP5; gemcitabine; multidrug resistance; pancreatic cancer.
Conflict of interest statement
The authors declare that they have no competing interests.
Figures
![Figure 1.](https://www.ncbi.nlm.nih.gov/pmc/articles/instance/10696546/bin/or-51-01-08666-g00.gif)
![Figure 2.](https://www.ncbi.nlm.nih.gov/pmc/articles/instance/10696546/bin/or-51-01-08666-g01.gif)
![Figure 3.](https://www.ncbi.nlm.nih.gov/pmc/articles/instance/10696546/bin/or-51-01-08666-g02.gif)
![Figure 4.](https://www.ncbi.nlm.nih.gov/pmc/articles/instance/10696546/bin/or-51-01-08666-g03.gif)
![Figure 5.](https://www.ncbi.nlm.nih.gov/pmc/articles/instance/10696546/bin/or-51-01-08666-g04.gif)
![Figure 6.](https://www.ncbi.nlm.nih.gov/pmc/articles/instance/10696546/bin/or-51-01-08666-g05.gif)
![Figure 7.](https://www.ncbi.nlm.nih.gov/pmc/articles/instance/10696546/bin/or-51-01-08666-g06.gif)
![Figure 8.](https://www.ncbi.nlm.nih.gov/pmc/articles/instance/10696546/bin/or-51-01-08666-g07.gif)
Similar articles
-
IFN‑γ induces apoptosis in gemcitabine‑resistant pancreatic cancer cells.Mol Med Rep. 2024 May;29(5):76. doi: 10.3892/mmr.2024.13200. Epub 2024 Mar 15. Mol Med Rep. 2024. PMID: 38488034 Free PMC article.
-
Interdependence of gemcitabine treatment, transporter expression, and resistance in human pancreatic carcinoma cells.Neoplasia. 2010 Sep;12(9):740-7. doi: 10.1593/neo.10576. Neoplasia. 2010. PMID: 20824050 Free PMC article.
-
TM4SF1 Promotes Gemcitabine Resistance of Pancreatic Cancer In Vitro and In Vivo.PLoS One. 2015 Dec 28;10(12):e0144969. doi: 10.1371/journal.pone.0144969. eCollection 2015. PLoS One. 2015. PMID: 26709920 Free PMC article.
-
[Mechanism of SPARC-enhanced chemosensitivity of pancreatic cancer cells to gemcitabine].Zhonghua Zhong Liu Za Zhi. 2014 May;36(5):335-40. Zhonghua Zhong Liu Za Zhi. 2014. PMID: 25030587 Chinese.
-
Inhibition of cancer cell growth in gemcitabine-resistant pancreatic carcinoma by mangiferin phytochemical involves induction of autophagy, endogenous ROS production, cell cycle disruption, mitochondrial mediated apoptosis and suppression of cancer cell migration and invasion.J BUON. 2019 Jul-Aug;24(4):1581-1586. J BUON. 2019. PMID: 31646812
Cited by
-
IFN‑γ induces apoptosis in gemcitabine‑resistant pancreatic cancer cells.Mol Med Rep. 2024 May;29(5):76. doi: 10.3892/mmr.2024.13200. Epub 2024 Mar 15. Mol Med Rep. 2024. PMID: 38488034 Free PMC article.
-
Early acquired resistance to EGFR-TKIs in lung adenocarcinomas before radiographic advanced identified by CT radiomic delta model based on two central studies.Sci Rep. 2023 Sep 20;13(1):15586. doi: 10.1038/s41598-023-42916-2. Sci Rep. 2023. PMID: 37730961 Free PMC article.