Clin Pediatr Hematol Oncol.  2007 Apr;14(1):53-63.

The Effect of Disodium Pamidronate on Human Osteosarcoma Cells

• Lee JA
• Shin HY
• Ahn HS

Abstract

PURPOSE: Disodium pamidronate (pamidronate) is a bisphosphonate (BP) and has been used to treat complications caused by metastatic bone tumors. The aim of this study was to assess the direct effect of pamidronate on human osteosarcoma cells and its interaction with bone growth factors.
METHODS
Three osteosarcoma cell lines (HOS, KHOS/NP, Saos-2) were treated with 100micrometer of pamidronate and changes in cell proliferation, cell cycle, and apoptotic markers were evaluated. To check the interaction of pamidronate with bone growth factors, KHOS/NP cells were maintained in serum-free culture medium for 24 hours. And then they were treated with Bone morphogenic protein (BMP)-2, insulin-like growth factor (IGF)-1, and platelet-derived growth factor (PDGF)-BB with or without pamidronate (100micrometer).
RESULTS
Seventy-two hours after pamidronate treatment, cell growth rate began to decrease by 93% for KHOS/NP, 54% for HOS, and 27% for Saos-2. And after 96 hours, growth of HOS and Saos-2 was decreased by more than 90%. We observed that pamidronate treatment changed the expression of cell cycle regulating proteins and induced cell cycle arrest at G1 phase. In apoptosis assay, loss of Bcl-2 (HOS) and appearance of BID, NBK (KHOS/NP) were observed after pamidronate treatment. Cleaved forms of caspase-3, -8, -9 and PARP were expressed in three cell lines after pamidronate treatment. When KHOS/NP cells were stimulated with bone growth factors, growth was increased by 124% for IGF-1, 102% for PDGF-BB, and 15% for BMP-2 compared to the control. But this stimulatory effect was offset when pamidronate was added together (82% for PDGF-BB, 77% for BMP-2 and IGF-1).
CONCLUSION
Pamidronate inhibited the proliferation of osteosarcoma cells and induced apoptosis. Also, pamidronate directly antagonized the stimulatory effect of bone growth factors. These data show the potential and impressive antitumor properties of pamidronate and call for application in the clinical setting.

Keyword

Osteosarcoma; Pamidronate; Apoptosis; Inhibition of cell proliferation; Bone growth factor

MeSH Terms

Apoptosis
Bone Development
Caspase 3
Cell Cycle
Cell Cycle Checkpoints
Cell Line
Cell Proliferation
G1 Phase
Humans*
Insulin-Like Growth Factor I
Osteosarcoma*
Platelet-Derived Growth Factor
Caspase 3
Insulin-Like Growth Factor I
Platelet-Derived Growth Factor