| Cancer is a common disease. With the success usage of anti-microtubules reagent in the adjuvant chemotherapy regimens for the late stage cancer patients, especially of paclitaxel, the interests of microtubule as the target of chemotherapy have been increased greatly nowdays. Microtubules are involved in many cellular processes besides mitosis. There're two subunit a and P, combining together to compose the heterodimers. The normal dynamic reorganization of the microtubule network is required for mitosis and cell proliferation, which is controlled by many factors.The major of the antimicrotubule reagents includes paclitaxel, docetaxel, vinblastine and vincristine. Paclitaxel, a plant antineoplastic agent from the bark of the Western yew, Taxus brevifolia Nut (Taxaceae), is widely used in the treatment of patients with ovarian and breast carcinoma. This drug has also shown effective results for many other solid tumors including lung, head and neck, bladder, and esophageal cancers. Previous studies indicated that paclitaxel is an unique antimicrotubule agent, acting on inhibiting microtubule depolymerization and promoting the formation of unusually stable microtubules, disrupting the normal dynamic reorganization of the microtubule network. Therefore the normal function of microtubule is broken, and thecell cycle progression in late G2/M phase is blocked via abnormal spindle formation. Then the cellular apoptosis is induced. The vinca alkaloid antimicrotubule agents, including vinblastine and vincristine, have been widely used as clinical anticancer agents for the treatment of leukemia, lymphomas, and some solid tumors. Vinca alkaloids could block the region involved in tubulin dimer attachment, and therefore prevent polymerization of microtubules with the blockage cell cycle progression at G2/M pahse. During recent years, several laboratories demonstrated that at clinically relevant concentrations antimicrotubule reagents could induce apoptotic cell death in a number of solid tumor cells, with typic DNA ladder of 180 bp and morphologic apoptotic changes. These results indicated that in addition to its classic activity against microtubule and cell cycle arrest, they also possessed cell-killing activity by induction of apoptosis. But with the difference of mechanisms of their function on the microtubule, the apoptosis must be induced through the different signal transduction pathway. However, the exact mechanisms by antimicrotubule reagents against tumor cells are not entirely clear. According to the previous study, the nuclear factor-KapppaB (NF-KB) contributes to the apoptosis in the solid tumor cells induced by antimicrotubule reagents.NF-kB, a member of Rel transcription factor family, binds with its specific intracellular inhibitor IkBα. They participate in the mediation or regulation of many biological processes, including inflammation, immune response, and cell proliferation, as well as apoptotic cell death. Upon certain stimulations, IkB-α is rapidly phosphorylated and degraded, allowing NF-KB to translocate to the nucleus, where it participates in transcriptional regulation of numerous genes. In this cascade of events IkB kinase complex, such as IKKα and IKKβ, is the key enzyme, which is responsible for the phosphorylation and degradation of IkB-α protein. To date, NF-kB has been reported to participate in the transcription of more than 150 target genes. Many of these NF-KB target genes are considered to be pro-apoptotic genes, such as FAS/APO-1 ligand (FasL), c-myc, ICE, and p53. It has been reported that theactivation of NF-kB is able to induce or block apoptosis, depending on different stimuli and different cell types.In this study, the aim is to explore the mechanisms of NF-KB pathway in the antimicrotubule reagents-induced apoptosis in solid tumor cells and the relationship between the NF-KB and G2/M phase arrest, and to detect the changes of the apoptotic-related genes which is down-stream or up-stream of NF-KB, It will help us to lear...
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