Low-dose zoledronate for the treatment of bone metastasis secondary to prostate cancer.
Bone metastases secondary to prostate
Cellular assays
Direct in vitro treatment
Low doses
Zoledronate
Journal
Cancer cell international
ISSN: 1475-2867
Titre abrégé: Cancer Cell Int
Pays: England
ID NLM: 101139795
Informations de publication
Date de publication:
2019
2019
Historique:
received:
27
09
2018
accepted:
01
02
2019
entrez:
22
2
2019
pubmed:
23
2
2019
medline:
23
2
2019
Statut:
epublish
Résumé
Bisphosphonates (BPs) including zoledronate (zol) have become standard care for bone metastases as they effectively inhibit tumor-induced osteolysis and associated pain. Several studies have also suggested that zol has direct anti-tumor activity. Systemic administration at high doses is the current approach to deliver zol, yet it has been associated with debilitating side effects. Local therapeutic delivery offers the ability to administer much lower total dosage, while at the same time maintaining sustained high-local drug concentration directly at the target treatment site. Here, we aimed to assess effects of lower doses of zol on bone metastases over a longer time. Prostate cancer cell line LAPC4 and prostate-induced bone metastasis cells were treated with zol at 1, 3 and 10 µM for 7 days. Following treatment, cell proliferation was assessed using Almarblue We show that treatment with 3-10 µM zol over 7-days significantly decreased cell proliferation in both the prostate cancer cell line LAPC4 and cells from spine metastases secondary to prostate cancer. Using the same low-dose and longer time course for treatment, we demonstrate that 10 µM zol also significantly inhibits tumor cell migration and 3D-cell growth/invasion. This project harnesses the potential of using zol at low doses for longer treatment periods, which may be a viable treatment modality when coupled with biomaterials or biodevices for local delivery.
Sections du résumé
BACKGROUND
BACKGROUND
Bisphosphonates (BPs) including zoledronate (zol) have become standard care for bone metastases as they effectively inhibit tumor-induced osteolysis and associated pain. Several studies have also suggested that zol has direct anti-tumor activity. Systemic administration at high doses is the current approach to deliver zol, yet it has been associated with debilitating side effects. Local therapeutic delivery offers the ability to administer much lower total dosage, while at the same time maintaining sustained high-local drug concentration directly at the target treatment site. Here, we aimed to assess effects of lower doses of zol on bone metastases over a longer time.
METHODS
METHODS
Prostate cancer cell line LAPC4 and prostate-induced bone metastasis cells were treated with zol at 1, 3 and 10 µM for 7 days. Following treatment, cell proliferation was assessed using Almarblue
RESULTS
RESULTS
We show that treatment with 3-10 µM zol over 7-days significantly decreased cell proliferation in both the prostate cancer cell line LAPC4 and cells from spine metastases secondary to prostate cancer. Using the same low-dose and longer time course for treatment, we demonstrate that 10 µM zol also significantly inhibits tumor cell migration and 3D-cell growth/invasion.
CONCLUSIONS
CONCLUSIONS
This project harnesses the potential of using zol at low doses for longer treatment periods, which may be a viable treatment modality when coupled with biomaterials or biodevices for local delivery.
Identifiants
pubmed: 30787671
doi: 10.1186/s12935-019-0745-x
pii: 745
pmc: PMC6368819
doi:
Types de publication
Journal Article
Langues
eng
Pagination
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