Zoledronic acid, a potent osteoclast inhibitor, induces apoptosis in osteoclasts by inhibiting enzymes of the mevalonate pathway and preventing the isoprenylation of small GTP-binding proteins such as Ras and Rho.
Zoledronic Acid is an intravenous, highly potent aminobisphosphonate approved worldwide, nitrogen-containing bisphosphonate. It is widely used in patients with osteoporosis or low bone mass to prevent or treat osteoporosis[1]. Zoledronic acid once yearly for up to 3 years in patients with primary or secondary osteoporosis significantly improved bone mineral density (BMD), reduced fracture risk and bone turnover. When treatment was continued for up to 6 years, additional benefits were seen, as evidenced by a reduced risk of vertebral fractures and higher BMD relative to 3 years' therapy. Zoledronic acid is also approved by FDA in 2007 for the treatment of postmenopausal osteoporosis[2]. Moreover, data from in vitro and pilot studies suggest that zoledronic acid also has antitumor activity including multiple myeloma and solid tumors with bone metastases. In vitro, 5.0 µmol/L zoledronic acid significantly inhibit HGF proliferation and promote its apoptosis rate[3]. In animal models, Zoledronic acid combination with anticancer therapies can increases apoptosis, inhibits tumor cell proliferation, and enhances immune surveillance[4]. Early studies of bone metastases have showed that low-dose zoledronic acid (30 μg/kg subcutaneous) can directly inhibit melanoma tumor bone growth in mice. In KRAS mutant cancers, it can enhance the efficacy of the MEK inhibitor trametinib, and disrupt the biological activity of RAS by suppressing its isoprenylation[5]. Zoledronic acid used along with cancer radiotherapy significantly decreased bone pain and improved the mean quality of life (QOL) in treating painful bone metastases from gastrointestinal cancers[6].
作用机制
Zoledronic Acid is an intravenous, highly potent aminobisphosphonate.
Zoledronic Acid 细胞研究
细胞系
浓度
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数据源
human foreskin fibroblast monolayer cells (HFF cells)
Growth inhibition assay
In vitro inhibitory concentration against the growth of Toxoplasma gondii in human foreskin fibroblast monolayer cells (HFF cells), IC50=0.79 μM
15857119
human Gamma delta T cells
Function assay
Effective concentration against human Gamma delta T cells, EC50=5.4 μM
15828834
human MCF7 cells
Proliferation assay
72 h
Antiproliferative activity against human MCF7 cells after 72 hrs by MTT assay, IC50=23 μM
24928399
human NCI-H460 cell
Proliferation assay
Antiproliferative activity against human NCI-H460 cell line by MTT assay, IC50=11.7 μM
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