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Detection of the Impact of Bisphosphonate on Multiple Myeloma using Lactadherin

Shuye Wang, Xiaomin Zhang, Jinxiao Hou, Yafeng Chen and Yueyue Fu

Background: Explore the impact of second-generation bisphosphonate drugs pamidronate on proliferation and apoptosis of human multiple myeloma cell line in vitro. Verify the synergistic effect of combination of pamidronate and melphalan on apoptosis of myeloma cells and demonstrate that lactadherin is the most effective probe for apoptosis detection.

Method: (1) Myeloma cells were treated with pamidronate or combination of melphalan and pamidronate at different concentrations. The cells were divided into 12 groups and treated with the drugs at intervals of 24 hours for 48 hours. After 48 hours treatment, inhibition rate of cell growth in different group were measured by MTT. (2) Two groups were treated with PBS buffer. PS exposure of the cells treated with drugs was detected using FITC-Annexin-V and FITC-lactadherin by flow cytometry.

Result: The increase of the proliferation and effect of apoptosis by pamidronate on multiple myeloma cells was parallel as the increase of pamidronate dose. In combination with melphalan, the effect of apoptosis induction was stronger than single drug group. PS exposure detected by lactadherin was significantly increased as the increase of amidronate concentration. PS exposure in treated group is more than that of control group.

Conclusion: Pamidronate exerts effects of growth inhibition and apoptosis induction on multiple myeloma cell in a dose-dependent way; Combination therapy increases apoptosis and exerts a synergistic effect; Lactadherin is the most effective probe in detecting myeloma cell apoptosis.