Mechanisms Of Bortezomib-mediated Radiosensitivity In Esophageal

Objective: Bortezomib is the first synthetic proteasome inhibitor. Esophagealcancer is one of the common malignant tumors in China, esophageal cancer patients inChina accounted for more than half of the world.To investigate the inhibitory effect ofBortezomib on human esophageal cancer cell lines and the sensibilization to ionizingradiation efficacy by Bortezomib.Methods: Three human esophageal cancer cell lines Eca-109, TE-1and KYSEwere utilized in this research.(1) MTT was used to detect cell viability afterpretreatment of Bortezomib at indicated concentrations for indicated periods of time.(2)Cell cycle distribution was analyzed after24h pretreatment of Bortezomib at differentconcentrations by flow cytometry.(3) Flow cytometry was also used to analyze cellapoptosis caused by Bortezomib at indicated concentrations.(4) Western blotting wasused to measure the protein level associated with cell apoptosis by pretreatment ofBortezomib.(5) Colony formation assay and MTT assay were applied to investigate theradiosensitivity of cancer cells.Results:(1) Bortezomib inhibited cell viability of three human esophageal cancercell lines in a dose-and time-dependent manner.(2) Enhancement of cell cycle arrest ofG2/M in Eca-109, TE-1and KYSE cells due to the treatment with Bortezomib for24h.(3) Bortezomib increased cell apoptosis in Eca-109and TE-1cells but not KYSE cellsafter24h treatment, cell apoptosis rate of KYSE cells was markedly increased byprolonging treatment to48h.(4) Bortezomib treatment led to an increase in Caspase-3protein level but a decrease in NF-κB protein level in Eca-109and TE-1cells.(5)Pretreatment of three human esophageal cancer cell lines with Bortezomib for24hbefore ionizing radiation potentiated the anticancer effect of IR, while no sensitizing toionizing radiation efficacy was found for48h pretreatment..Conclusions:(1) Bortezomib suppressed cancer cell viability in all cell lines tested,the cytotoxicity was dose-and time-dependent.(2) Bortezomib enhanced cell cyclearrest of G2/M in three human esophageal cancer cell lines.(3) Bortezomib induced cellapoptosis in Eca-109, TE-1and KYSE cells.(4) Bortezomib may induce cell apoptosis by inhibiting NF-κB expression.(5) Bortezomib potentiated the anticancer effect of IRin a short-term, while no clearly long-term effect was observed.