The Expression Level Of Human Serine/Threonine Kinase33Gene Effect On Signaling Pathway PI3K/AKT、JAK/STAT In NSCLC

Objective To investigate the expression level of human serine/threonine kinase33gene (STK33) effect on transferring signaling pathway PI3K/AKT and JAK/STAT in non small cell lung cancer(NSCLC). Figure out the molecules mechanisms which STK33enhance the invasion and metastasis capacity of NSCLC and suggest a new therapeutic targets and theoretical support for NSCLC therapy.Methods Developed NSCLC cells L9981which high metastatic ability and low metastatic ability NL9980. Detected the level of STK33expression and STK33protein by real time polymerase chain reaction (RT-PCR) or Western-blotting. And then the NL9980were transacted by the constructed STK33plasmid high expression. The L9981were transacted by the STK33plasmid low expression. After the transfection was insured, the level of important protein AKT, mTOR, JAK and STAT3as well as the phosphorylation level in PI3K/AKT and JAK/STAT signaling pathways of four groups cells was detected by Western-blottingResults The expression level of STK33in NL9980was lower than L9981cells (P<0.05). The amount of STK33protein in NL9980was lower than L9981.Plasmids which the STK33gene was expressed highly were built and the NL9980were transferred successfully. Plasmids which the STK33gene was expressed lowly were built and the L9981were transferred successfully. The expression level of STK33in NL9980was increased (P<0.05) because of the transacting of plasmids which the STK33gene was raised highly. The expression level of STK33in L9980was decreased (P<0.05) thanks to the transacting of plasmids which the STK33gene was expressed lowly. The level of non-phosphorylated protein AKT, mTOR, JAK, STAT3 in PI3K/AKT, JAK/STAT signaling pathway was not little changed through Western-blotting.Expression levels of phosphocreatine protein showed an overall change. When expression level of STK33was regulated positively, the amount of phosphocreatine protein AKT, mTOR, JAK, STAT3in NL9980(+) was more than NL9980. When the expression level of STK33was downregulated, the amount of phosphocreatine protein AKT, mTOR, JAK, STAT3in L9981(-) was under than L9981.Conclusions The level of significant phosphorylation protein will be changed because the changes of STK33expression level. Elevated expression of STK33may lead the amount of phosphorylation protein AKT, mTOR, JAK, STAT3be increased. Then the EMT, neovascularization, muscle fiber protein remodeling, immune escape of tumor cells should be enhanced. Thereby the invasion and metastasis of NSCLC will be strengthened.Inhibit the expression of STK33or STK33kinase activity may reduce the transfer ability of NSCLC.This approach may become a new breakthrough of targeted therapy for NSCLC.