Effects of proteasome inhibitors on apoptosis of undifferentiated thyroid cancer cells and its mechanism

OBJECTIVE: To investigate the role of 150-kD oxygen-regulated protein(ORP150) in thyroid cancer cell death induced by proteasome inhibitors.METHODS: The undifferentiated thyroidcancer FRO cells were treated with vehicle,proteasome inhibitor Lactacystin,PSI,Epoxomycin and MG132;OPR150 expression levels were knockdown by RNA interference;OPR150 mRNA and protein levels were analyzed by using real time RT-PCR and Western blot,respectively;the apoptotic rate was analyzed by using flow cytometry(FCM).RESULTS: MG132,PSI,Epoxomycin and Lactacystin significantly increased the mRNA and protein levels of ORP150(P0.01) in undifferentiated thyroid cancer FRO cells;small interfering RNA against ORP(siORP150) markedly reduced the ORP150 mRNA and protein levels when compared with vehicle or scramble siRNA(P0.01),in addition,siORP150 dramatically increased Lactacystin,PSI,Epoxomycin and MG132 mediated increase in apoptotic cells(P0.01).CONCLUSION: Proteasome inhibitors increase the ORP150 expression in undifferentiated thyroid cancer FRO cells,and the suppression of ORP150 expression by siORP150 significantly enhances the apoptosis of FRO cells induced by proteasome inhibitors.