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Identification of chemoresistance‐related mRNAs based on gemcitabine‐resistant pancreatic cancer cell lines
- Source :
- Cancer Medicine, Cancer Medicine, Vol 9, Iss 3, Pp 1115-1130 (2020)
- Publication Year :
- 2019
- Publisher :
- John Wiley and Sons Inc., 2019.
-
Abstract
- Gemcitabine (GEM) alone and GEM‐based chemotherapy are the preferred regimens for treating advanced unresectable and metastatic pancreatic cancer (PC). However, these treatments have limited efficacy due to acquired resistance of cancer cells to chemotherapy, the mechanisms of which are not fully understood. In this study, we established two stable multidrug‐resistant cell lines, BxPC‐3‐GR and CFPAC‐1‐GR, from their corresponding parental cells through exposure to GEM following a stepwise incremental dosing strategy. The GEM IC50 values of BxPC‐3‐GR and CFPAC‐1‐GR increased 112‐fold and 210‐fold, respectively, compared to parental cell lines. In vitro and in vivo experiments confirmed that both GEM‐resistant cell subgroups declined in proliferative capacity, but were more resistant to GEM. Unlike CFPAC‐1‐GR, BxPC‐3‐GR exhibited enhanced migratory and invasive properties compared with BxPC‐3 in vitro. We also compared differentially expressed mRNA profiles between parental and GEM‐resistant cells using transcriptome sequencing. RRM1, STIM1, and TRIM21 were significantly upregulated in both GEM‐resistant cell lines and confirmed to be associated with the degree of GEM resistance by quantitative reverse‐transcription polymerase chain reaction and western blot analysis. These three genes were more highly expressed in PC tissues and potentially regarded as prognostic biomarkers through database mining. Thus, our findings provide chemo‐resistant cell models to better understand the underlying mechanisms of chemoresistance, and to explore potential biomarkers for GEM response in PC patients.<br />Our findings provide chemo‐resistant cell models to better understand the underlying mechanisms of chemoresistance and to explore potential biomarkers for gemcitabine response in pancreatic cancer patients
- Subjects :
- 0301 basic medicine
Cancer Research
endocrine system diseases
medicine.medical_treatment
Cell
pancreatic cancer
Deoxycytidine
Mice
0302 clinical medicine
RNA-Seq
Original Research
Cancer Biology
GEM‐resistant cell lines
lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens
Neoplasm Proteins
Up-Regulation
Gene Expression Regulation, Neoplastic
medicine.anatomical_structure
Oncology
Ribonucleoproteins
030220 oncology & carcinogenesis
RRM1
medicine.drug
Ribonucleoside Diphosphate Reductase
STIM1
Biology
lcsh:RC254-282
03 medical and health sciences
In vivo
Pancreatic cancer
Cell Line, Tumor
medicine
Biomarkers, Tumor
Animals
Humans
Radiology, Nuclear Medicine and imaging
RNA, Messenger
Stromal Interaction Molecule 1
Chemotherapy
medicine.disease
Xenograft Model Antitumor Assays
Gemcitabine
In vitro
Pancreatic Neoplasms
030104 developmental biology
Cell culture
Drug Resistance, Neoplasm
Cancer cell
Cancer research
TRIM21
Subjects
Details
- Language :
- English
- ISSN :
- 20457634
- Volume :
- 9
- Issue :
- 3
- Database :
- OpenAIRE
- Journal :
- Cancer Medicine
- Accession number :
- edsair.doi.dedup.....effa5f12de0a3f2184510de16302deef