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Low-dose zoledronic acid reduces spinal cord metastasis in pulmonary adenocarcinoma with neuroendocrine differentiation.
- Source :
-
Anti-cancer drugs [Anticancer Drugs] 2012 Oct; Vol. 23 (9), pp. 970-8. - Publication Year :
- 2012
-
Abstract
- Zoledronic acid (ZOL), a nitrogen-containing compound, is effective in the treatment of skeletal disorders, but its long-term use in high doses gives rise to complications such as osteonecrosis. We aimed to investigate the effect of low-dose ZOL on the expression of the neural cell adhesion molecule (NCAM), which may be correlated with tumor growth and spinal cord metastasis in lung adenocarcinoma with neuroendocrine differentiation. First, we used the small hairpin RNA technique to directly knock down NCAM expression in cells of a murine lung adenocarcinoma line, line 1 cells, and found that the tumor cells generated showed lower invasive capacity, slower tumor growth, and lesser tendency for spinal cord metastasis than control cells. Further, ZOL decreased NCAM expression and invasiveness in line 1 tumor cells in vitro. Line 1/lacZ cells, a stable clone tagged with the lacZ gene, were introduced into mice, followed by ZOL treatment (1 μg/kg/weekly). Low-dose ZOL significantly reduced spinal cord metastasis probably through reduced NCAM expression in vivo. These findings indicated that NCAM is involved in tumor growth and spinal cord metastasis of lung adenocarcinoma with neuroendocrine differentiation. Treatment with low-dose ZOL can reduce NCAM expression that may contribute toward reduced spinal cord metastasis, suggesting that NCAM is an alternative therapeutic target and that the low-dose ZOL treatment protocol is a reasonable approach for its treatment.
- Subjects :
- Animals
Antineoplastic Agents administration & dosage
Antineoplastic Agents pharmacology
Carcinoma, Neuroendocrine metabolism
Carcinoma, Neuroendocrine secondary
Cell Differentiation
Cell Line, Tumor
Cloning, Molecular
Diphosphonates administration & dosage
Diphosphonates pharmacology
Dose-Response Relationship, Drug
Flow Cytometry
Gene Knockdown Techniques
Green Fluorescent Proteins genetics
Imidazoles administration & dosage
Imidazoles pharmacology
Lung Neoplasms metabolism
Lung Neoplasms pathology
Mice
Mice, Inbred BALB C
Neoplasm Invasiveness
Neoplasm Transplantation
Neural Cell Adhesion Molecules biosynthesis
Neural Cell Adhesion Molecules genetics
RNA, Small Interfering genetics
Spinal Cord Neoplasms metabolism
Spinal Cord Neoplasms secondary
Transfection
Zoledronic Acid
Antineoplastic Agents therapeutic use
Carcinoma, Neuroendocrine drug therapy
Diphosphonates therapeutic use
Imidazoles therapeutic use
Lung Neoplasms drug therapy
Neural Cell Adhesion Molecules antagonists & inhibitors
Spinal Cord Neoplasms drug therapy
Subjects
Details
- Language :
- English
- ISSN :
- 1473-5741
- Volume :
- 23
- Issue :
- 9
- Database :
- MEDLINE
- Journal :
- Anti-cancer drugs
- Publication Type :
- Academic Journal
- Accession number :
- 22713592
- Full Text :
- https://doi.org/10.1097/CAD.0b013e328355f0ec