【摘 要】
：
Diffuse large B-cell lymphoma (DLBCL) is the most common non-Hodgkin lyrnphoma in North America.Response rate of DLBCL to the current empirically developed chemotherapy is only 50-60%.The need for dev
【机 构】
：
Hematopathology Laboratory University of Maryland School of Medicine Baltimore USA
【出 处】
：
BIT‘s2nd Annual World Cancer Congess-2009 (2009第二届癌症大会)
论文部分内容阅读
Diffuse large B-cell lymphoma (DLBCL) is the most common non-Hodgkin lyrnphoma in North America.Response rate of DLBCL to the current empirically developed chemotherapy is only 50-60%.The need for development of innovative therapies against DLBCL is urgent.New therapies depend on the development of new therapeutic agents and/or discovery of novel molecular targets.We have identified the high levels ofphospho-p70S6K and cdc2/cdk1 in the vast majority of DLBCL patient specimens analyzed (n=38), and hypothesized that phospho-p70S6K and cdc2/cdk1 were potential molecular targets for combination therapy of DLBCL.Since phospho-p70S6K and cdc2/cdk1 are protein kinases involved in the PI3K/Akt/mTOR signal transduction pathway and eell cycle progression, we tested the combined effects ofrapamycin and UCN-01, two agents that inhibit the phosphorylation of p70S6K/p85S6K, Akt and cdc2/cdk1, respectively, in several DLBCL cell lines.The results showed that while single agents had only variable inhibitory effects on the DLBCL cells, combined rapamycin and UCN-01 synergistically inhibited DLBCL proliferation by inducing G1 arrest and apoptosis of DLBCL.Inhibition of DLBCL cell proliferation is through suppressing the phosphorylation of p70S6K/p85S6K and CDC2 expression.Our findings suggest that phospho-p70S6K/p85S6K and cdc2/cdkl are novel molecular targets for DLBCL chemotherapy.Simultaneously targeting phospho-p70S6K/p85S6K and cdc2/cdk1 is very effective in inhibiting DLBCL proliferation and overcoming drug resistance.This work also suggests that multi-level inhibition of PI3K/Ak/mTOR pathway and double block of cell cycle progression at (G1 and G2 checkpoints are effective strategies for DLBCL therapy.
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