Proliferation Inhibition And Radiosensitivity Of Protein Kinase Inhibitor Tamoxifen On Human Glioma Cells

Objective: In this study, we explored the protein kinase C (PKC) inhibitor TAM incombination with X-rays on the growth, cell cycle, apoptosis and radiosensitivity ofglioma cells, constructed tumor-bearing mouse model with A172cells to evaluate theradiosensitivity of TAM in vivo.Methods: Glioma cell viability was detected by MTT assay; Scrath migrationassay was used to determine the migration ability of glioma cells; Colony-forming assaywas performed to assess the radiosensitization of TAM on glioma cells; Changes ofglioma cell cycle distribution and cell apoptosis were analyzed by flow cytometry assay;Western-blot was used to detected the expression level of related proteins; Constructiontumor-bearing mouse with A172cells. Volume of the tumor was evaluated by MRIbefore and after the treatment of TAM and/or IR. Immunohistochemistry was used todetermine the expression of Bad in tumor.Results: TAM inhibited cell growth of A172and U251cells in a dose-andtime-dependent manner (p<0.01); TAM combined with radiation suppressed themigration of A172and U251cells compared to control; Colony-forming assay showedTAM enhanced radiosensitivity of A172and U251cells. TAM enhanced radiationinduced G2/M arrest and apoptosis of A172and U251cells (p<0.05); The activity ofPKCι and Cdk7were inhibited by TAM. The expression of Bad was increased whileCyclinB1was decreased. Caspase3and PARP were activated by TAM and radiation.MRI showed that TAM combined with radiation significantly reduced tumor volume.Conclusions: TAM inhibits the proliferation of human glioma cells and enhancesradiosensitivity in glioma cells. The migration ability of A172and U251was suppressedby TAM. TAM enhances radiation-induced cell cycle arrest of G2/M in A172and U251cells, accompanying a significant decrease of CyclinB1. TAM enhancesradiation-induced apoptosis with a markedly increase of Bad expression, increases theactivation of caspase3and reduces the activation of PARP. Current study demonstrated that TAM enhances the radiosensitivity of glioma cells through inhibition the activity ofPKCι and Cdk7. TAM combined with radiotherapy can effectively inhibit tumorproliferation in vivo.