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The Construction Of Expressing Vector ShRNA/mdr1 And A Study On Multidrug Resistance Reversal Of Human Hepatocellular Carcinoma By RNA Interference

Posted on:2007-10-26Degree:DoctorType:Dissertation
Country:ChinaCandidate:G D PanFull Text:PDF
GTID:1104360185494724Subject:Surgery
Abstract/Summary:PDF Full Text Request
BACKGROUND Hepatocellular carcinoma (HCC) is common in China with increasing mobidity and the second mortality of malignant cancer. HCC is often diagnosed in terminal stage, which is only 30%~40% of them indicated for radical operation because of its unique biology. Therefore, most of the HCC patients need to be treated by chemotherapy and interventing chemotherapy to improve their outcome. However, multidrug resistance (MDR) resulting from the chemotherapy hinders the prognosis of HCC.In order to reverse the MDR of HCC, scientist has been working hard to search efficient measurements such as inhibitors of P-glycoprotein (P-gp), oligonucleotide, antisense RNA techniques and other techniques in regulating MDR-related gene expression. These measurements failed to be applied in clinics because of their low efficiency and speciality, insertional mutagenesis, cis-activation of silent genes by their strong promoters. RNA interference (RNAi) is a recently new approach of gene therapy, whose principal is that RISC (RNA induced silencing complex-consisted of endogenous or exogenous duplex short RNA and incision enzyme) identifies and shears its homologous gene of siRNA, thus degradating sequence specific mRNA and suppressing the targeted gene expression. RNAi is charactered by high specificity, heritage, diffusivity and posttranscriptional suppression. Many reports showed that siRNA/mdr1 could effectively reverse the MDR of several kinds of cancer cells in vivo and in vitro. As our knowledge, there is no reports about the effect of RNAi on HCC MDR. To investigate the possibility of reversal of HCC MDR by RNAi, we perform this study to search a new gene therapeutic measurement for improving the outcome of HCC.
Keywords/Search Tags:RNA interference, Multidrug resistance, plasmid vevtor, Hepatocellular carcinoma
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