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siRNA Against mTOR Influence on HepG2 Cells in Vivo

Author: GuZuo
Tutor: ZhangYangDe
School: Central South University
Course: Biomedical Engineering
Keywords: mTOR p70S6K siRNA Hepatic carcinoma Rapamycin Apoptosis Ability of tumor invasion
CLC: R735.7
Type: Master's thesis
Year: 2011
Downloads: 96
Quote: 0
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Abstract


Objective:The mammalian target of rapamycin(mTOR)that is an evolutionarily conserved serine-threonine kinase of a 289-kDa in length belongs to the PIKK [phosphoinositide 3-kinase(P13K)-related kinase]family. mTOR signaling pathway is frequently activated in human cancers. In mammals, the two best-characterized targets of mTOR are the ribosomal S6 kinases and the eukaryotic inifiation factor(elF4E)-binding protein 1(4E-BP1). mTOR activation leads the phosphorylations of S6K and 4EBP1. The latter releases from the cap-dependent translation initiation factor e1F4E, ultimately resulting in enhanced translation from subset of genes required for cell growth. These two events lead to an increase in ribosomal biogenesis and the selective Translation of special mRNA populations.mTOR has recently been recognized as an important and attractive therapeutic target for cancer therapy. The potential applications of mTOR inhibitors for treating various cancers including renal, prostate, breast, pancreatic, and lung cancers, etc, have been actively studied both preclinically and clinically. However, the mTOR/p70S6K signaling pathway in HCC has not been investigated so far,which impel the authors to investigate the role of mTOR/p70S6K signaling pathway for finding a novel target for the anticancer drugs in HCC. In the present study,we investigated the activated mTOR and its major downstream members in HCC cell lines HepG2, as well as the changes of mRNA and protein expression levels, apoptosis in the HCC cells treated with rapamycin and small interference RNA(siRNA)against mTOR(mTOR-siRNA).Methods:1、mTOR/p70S6K activated in HCC using western blott, detection of mTOR, expression of different proteins invasion.2、mTOR-siRNA in HepG2 mTOR/p70S6K signaling pathway and cell growth and proliferation in vitro Immunohistochemistry and RT-PCR and other methods of transfection efficiency of HepG2 cell proliferation and apoptosis were detected.3、mTOR-siRNA on HepG2 cells in human liver cancer cell invasion in vitro The use of Transwell to evaluate cell invasion.Results:1、mTOR-siRNA HepG2 cells increased rapamycin sensitivity.2、HepG2 in mTOR, p70S6K, p-p70S6K proteins were expressed.3、mTOR-siRNA inhibited proliferation and invasion of tumor cells.Conclusion:Rapamycin can specifically block the signaling pathway mTOR/p70S6K hepatoma cells, and inhibit the expression of mTOR reduced p70S6K, inhibits cell proliferation and induced apoptosis. And also increased cell sensitivity to rapamycin. Show that the activation of mTOR/p70S6K signaling pathway may be the treatment of liver cancer drug targeting is an important molecular target.mTOR-siRNA can promote apoptosis and inhibit tumor growth, and can improve the cells to rapamycin sensitivity. Both can be effective in vivo inhibition of mTOR/p70S6K signaling pathway, reduced the expression of mTOR, and inhibition of p70S6K phosphorylation.

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