Bortezomib could down-regulate the expression of RANKL, inhibit cell proliferation and induce cell apoptosis in the human myeloma cell line RPMI 8226 by activating casepase-3

作者：Lin, Li; Chen, Dong; Xiang, Zhen-Fei; Pei, Ren-Zhi; Zhang, Pi-Sheng; Liu, Xu-Hui; Du, Xiao-Hong; Lu, Ying^*

来源：Cancer Biomarkers, 2017, 20(2): 217-224.

DOI：10.3233/CBM-170584

• Proteasome inhibitor
• bortezomib
• receptor activator of NF-kappa B ligand
• multiple myeloma
• RPMI 8226
• cell proliferation
• cell apoptosis

OBJECTIVE: In spite of bortezomib being developed and demonstrated as a safe drug therapy for multiple myeloma (MM), the role of bortezomib-induced receptor activator of nuclear factor (NF)-kappa B ligand (RANKL) in the MM cell lines remains to be understood. Thus the present study aims to explore the impact of bortezomib on RANKL expression, cell growth and apoptosis in human myeloma cell line RPMI 8226. @@@ METHODS: Four experiment groups were set according to different concentrations of bortezomib, namely blank group (treated with DMEM solution free of other drugs), low-dose group (treated with 10 nmol/L bortezomib), middle-dose group (treated with 20 nmol/L bortezomib) and high-dose group (treated with 40 nmol/L bortezomib). Western blotting was adopted to detect RANKL protein expression. MTT assay was performed to detect cell proliferation. Flow cytometry was used to analyze cell cycle and apoptosis. Spectrophotometry was applied to determine caspases-3 activity. @@@ RESULTS: Compared with the blank group, the RANKL protein expression, cell number at the S stage was reduced while cell inhibition rate, cell apoptosis rate and caspase-3 activity enhanced remarkably in the low-dose, middle-dose and high-dose groups with dose-dependent manner. Compared with those treated with bortezomib (20 nmol/L and 40 nmol/L) for 6 h, the RANKL expression was down-regulated, cell inhibition rate was increased, cells at the S stage were reduced, cell apoptosis rate was enhanced, and caspase-3 activity elevated in the RPMI 8226 cells as treated with bortezomib for 24 h, with a dose- and time-dependent manner. @@@ CONCLUSIONS: Bortezomib could reduce the RANKL expression, inhibit cell proliferation and activate caspase-3 activity to induce cell apoptosis in RPMI 8266 cells.

• 出版日期2017
• 单位宁波市医疗中心李惠利医院; 宁波大学