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Gene expression analysis for predicting gemcitabine sensitivity in pancreatic cancer patients.

ABSTRACT: BACKGROUND/AIMS: Current in vitro drug sensitivity tests have limitations and disadvantages. This study investigated the use of gene expression data to predict the sensitivity of pancreatic cancers to gemcitabine. MATERIALS AND METHODS: Cancer cells isolated from 14 pancreatic cancer patients were tested in vitro for gemcitabine sensitivity using the collagen droplet drug sensitivity test (CD-DST). On the basis of this test, 9 of the 14 cancers were identified as either gemcitabine-sensitive or gemcitabine-resistant. Total RNA was extracted from each of those nine cancers and used as a template to synthesize Cy3-labeled cDNA. Pancreatic RNA extracted from six normal individuals was used as a control. Labeled probes were hybridized to an Atlas Glass Human 1.0 Microarray chip, after which the chips were washed and scanned, and the data were analyzed using Microsoft Excel-embedded software. The expression profiles of selected genes were confirmed using real-time PCR analysis. RESULTS: Statistical analysis of the microarray data showed that four genes were differentially expressed in gemcitabine-sensitive cancers: microsomal glutathione S-transferase 1 (GSTT1), topoisomerase II alpha (TOP2A), caspase 3, and ATP-binding cassette and subfamily C member 2 (ABCC2). More than 20 other genes were additionally identified as possible candidate genes associated with drug resistance. CONCLUSIONS: Expression of drug resistance-related genes appeared to predict whether a cancer was gemcitabine-sensitive or -resistant. Further study will enable a drug resistance scoring system to be established on the basis of gene expression. Such a system will allow more efficient application of chemotherapy.

SUBMITTER: Bai J

PROVIDER: S-EPMC2020785 | biostudies-other | 2007

REPOSITORIES: biostudies-other

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microRNA-218 promotes gemcitabine sensitivity in human pancreatic cancer cells by regulating HMGB1 expression.

Project description:ObjectiveThe purpose of this study was to examine the effect of gemcitabine (GEM) on microRNA-218 (miR-218) expression in human pancreatic cancer cells.MethodsQuantitative reverse transcription polymerase chain reaction (qRT-PCR) was performed to examine the differences in miR-218 expression between the GEM-sensitive BxPC-3 pancreatic cancer cells and GEM-resistant PANC-1 cells. The effect of GEM on the expression of miR-218 in PANC-1 cells was also investigated. PANC-1 cells were transfected either with HMGB1 siRNA to knock down the expression of HMGB1 or with the recombinant HMGB1 expression vector (pcDNA3.1-HMGB1) to overexpress HMGB1. The effect of ectopic expression of HMGB1 on the apoptosis of miR-218-transfected and GEM-treated PANC-1 cells was examined by flow cytometric analysis.ResultsThe miR-218 expression level was lower in GEM-resistant PANC-1 cells compared to GEM-sensitive BxPC-3 cells (P<0.05). The percentage of apoptotic PANC-1 cells was significantly increased in the miR-218 mimic + GEM group compared to the mimic ctrl + GEM group and the normal control group (P<0.01). The HMGB1 expression level was markedly decreased in PANC-1 cells transfected with HMGB1 siRNA but was significantly increased in PANC-1 cells transfected with the recombinant HMGB1 expression vector, pcDNA3.1-HMGB1 (P<0.01). The proportion of apoptotic PANC-1 cells was significantly lower in the miR-218 mimic + GEM + pcDNA3.1-HMGB1 group compared to the miR-218 mimic + GEM + HMGB1 siRNA group (P<0.01).ConclusionsThe expression level of miR-218 was downregulated in the GEM-resistant cell line. miR-218 promoted the sensitivity of PANC-1 cells to GEM, which was achieved mainly through regulating the expression of HMGB1 in PANC-1 cells.

| S-EPMC4490198 | biostudies-literature

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