| Summary: | 碩士 === 中國醫藥學院 === 中國藥學研究所 === 91 === The central components of the cell-cycle regulatory system are cyclin-dependent kinases（Cdks）, whose activity depends on association with regulatory proteins called cyclins. Oscillations in the activities of various cyclin-Cdk complexes leads to the initiation of various cell-cycle events. For instance﹐activation of cyclin D-Cdk4/6 and cyclin E-Cdk2 makes the cell-cycle progress from G1 into S phase. However, the activities of cyclin-Cdk complexes can be suppressed by the binding of Cdk inhibitor proteins（CdkIs）. Then﹐the progression of cell-cycle may be paused.
Berberine, an isoquinoline plant alkaloid﹐has multiple pharmacological actions﹐including anti-inflammatory and anti-microbial activities. Although berberine had been demonstrated to have antineoplastic function on leukemia﹐gastric and esophageal cancer cells. Little is known about the cellular and molecular mechanisms of antitumor effect of berberine. In this study, human NSCLC cell lines H1299 and H1299/p53 were used to examine the antitumor effect of berberine. Treatment with berberine caused a dose-dependent growth inhibition. Data from flow cytometry analysis indicated that berberine-mediated antiproliferation effect related to G1 phase arrest. Moreover, this berberine-induced growth inhibition was associated with decrease the expression levels of cyclin D3、Cdk2 and Cdk4 proteins and increase in cyclin E、p16 and p21 protein. In vitro kinase assay indicated that berberine inhibited the Cdk2 and Cdk4 kinase activities and consequently lead to hypophosphorylated of retinoblastoma protein-p130. In addition﹐decrease in ERK protein level and activity is also observed. Taken together, berberine can inhibit cancer cell growth by directly modulating the expression of mutiple cell cycle regulatory molecules, such as cyclins、Cdks and CdkIs. These results suggest that berberine may be used as a potent agent for cancer therapy.
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