Low-dose zoledronic acid reduces spinal cord metastasis in pulmonary adenocarcinoma with neuroendocrine differentiation

Ying Ying Li, John W C Chang, Ling Ling Hsieh, Shu Mei Chen, Kun Yun Yeh

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2 Citations (Scopus)


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.

Original languageEnglish
Pages (from-to)970-978
Number of pages9
JournalAnti-Cancer Drugs
Issue number9
Publication statusPublished - Oct 1 2012
Externally publishedYes



  • lung adenocarcinoma
  • neural cell adhesion molecule
  • neuroendocrine differentiation
  • spinal cord metastasis
  • zoledronic acid

ASJC Scopus subject areas

  • Pharmacology
  • Pharmacology (medical)
  • Cancer Research
  • Oncology

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