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Involvement of MicroRNA-451in Chemosensitivity of Pancreatic Cancer Cells to Gemcitabine

Author: FuJi
Tutor: ZhaoYuPei
School: Beijing Union Medical College
Course: Clinical
Keywords: pancreatic cancer microRNAs gemcitabine sensitivity
CLC: R735.9
Type: PhD thesis
Year: 2012
Downloads: 64
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Abstract


BackgroundPancreatic cancer is characterized by poor prognosis in digestive system malignancies. Most of the clinic patients are in late stage, only15%of them got the chance of operation, but the5-year survival rate is less than10%. The first line chemotherapy drug is DNA chain terminator gemcitabine. Even this drug, the objective response rate is less than20%in the clinic. This broad spectrum of drug resistance is inherent to pancreatic cancer itself. Therefore, the understanding of molecular mechanisms of chemoresistance in pancreatic cancer is current research focus.MicroRNAs are a novel group of short RNAs, about22nucleotide in length, that regulate gene expression in a posttranscriptional manner by pairing with complementary nucleotide sequences in3’UTR of target mRNA. Abnormal expression of microRNAs is linked with cancer development and progression.After reviewing the literature found in breast cancer, non-small cell lung cancer, colorectal cancer, microRNA-451adjust different cancer chemosensitivity through different ways. Previous study use microRNAs chips found the expression of microRNA-451is different in chemoresistant and parental pancreatic cancer strains. So this experiment will investigate the impact of microRNA-451on the chemoresistance of pancreatic cancer cell strains.Objective1Confirm the differential expression of microRNA-451in parental pancreatic cancer cell strain and chemoresistant strain.2Investigate chemosensitivity changes in pancreatic cancer cell strains which is transfected with microRNA-451mimics and inhibitor.3Explore the mechanism of microRNA-451infect chemosensitivity to gemcitabine in pancreatic cancer cell strains. Method1Through RT-qPCR to confirm the different expression of microRNA-451in SW1990parental cell strain and gemcitabine-resistant cell strain.2Use lipofectamine2000transfect microRNA-451mimics and inhibitor to pancreatic cancer cell line SW1990and MIA-PaCa2, verify transfection efficiency, then use CCK-8kit assay the inhibition rate of pancreatic cancer cells, which was treated with different concentrations of gemcitabine.3Use Annexin V/PI staining, caspase-3activity assay and Western Blot investigate the apoptosis rate of pancreatic cells, in order to explain the mechanism of pancreatic cell chemoresistance changes caused by microRNA-451.Result1The expression of microRNA-451is down regulated in SW1990-gemcitabine resistance cell strain compare with the parental cell strain.2The increased level of microRNA-451can improve gemcitabine treatment, with lower level reduce the chemosensitivity. This results were repeated in two pancreatic cancer cell lines MIA-PaCa2and SW1990for four times.3The rate of pancreatic cancer cell apoptosis is promoted by microRNA-451mimics and reduced by microRNA-451inhibitor.ConclusionMicroRNA-451improve the chemosensitivity of pancreatic cancer cells by promoting apoptosis induced by gemcitabine.

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CLC: > Medicine, health > Oncology > Gastrointestinal Cancer > Pancreatic tumors
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