Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2011 Apr;44(2):139-46.
doi: 10.1111/j.1365-2184.2011.00745.x.

Anti-tumour and anti-angiogenetic effects of zoledronic acid on human non-small-cell lung cancer cell line

M Di Salvatore  1 , A Orlandi, C Bagalà, M Quirino, A Cassano, A Astone, C Barone
Affiliations

Anti-tumour and anti-angiogenetic effects of zoledronic acid on human non-small-cell lung cancer cell line

M Di Salvatore et al. Cell Prolif. 2011 Apr.

Abstract

Objectives: Although emerging data suggest that zoledronic acid (Zol) may have different anti-tumour activities against a broad range of cancers, its effects on lung cancer remain largely unknown. The aim of this study was to evaluate in vitro the anti-tumoural and anti-angiogenetic effect of zoledronic acid in non-small-cell lung cancer (NSCLC) cells.

Material and methods: We treated A549 NSCLC cells with zoledronic acid to investigate survival, cell cycle activity, anti-angiogenic activity and apoptotic responses to it.

Results: We observed that highest Zol concentration (100μm) caused arrest in G1 phase of the cell cycle and also induced different percentages of apoptosis in presence (0.9% versus 4.4%) or absence (2.4% versus 28.5%) of serum (P=0.0001). Zol concentration from 5 to 100μm for 2 days induced significant concentration-dependent cell death in adherent cells. Furthermore, Zol (10-100μm) induced dose-dependent reduction both of mRNA and protein expression of VEGF associated with parallel decrease in VEGF secretion in the culture medium.

Conclusion: Taken together, these results support a possible anti-cancer and anti-angiogenetic activity of Zol. Our data may not only provide a basis for the clinical use of this drug as preventive agent of bone metastases but also suggest that Zol deserves attention as an anti-cancer agent in non-small-cell lung cancer.

PubMed Disclaimer

Figures

Figure 1
Figure 1
Zol induces dose‐dependent reduction of viability of A549 and 95D cells. (a) MTT cytotoxic assay of serum‐incubated A549 and 95D cells. (b) MTT cytotoxic assay of starved A549 and 95D cells.
Figure 2
Figure 2
Zol induces cell cycle arrest and apoptosis. (a) Cell cycle analysis of A549 cells treated with Zol in presence of serum. (b) Cell cycle analysis of A549 cells starved and treated with Zol. (c) Apoptosis of A549 cells evaluated by annexin V flow cytometric analysis.
Figure 3
Figure 3
Zol effect on cyclins and survivin. (a) Zol significant down‐regulation of Cyclin D1. (b) Zol significant down‐regulation of cyclin B1. (c) Zol significant down‐regulation of survivin.
Figure 4
Figure 4
Zol reduces expression and secretion of VEGF. (a) Zol significant down‐regulation of VEGF mRNA. (b) Concentration‐course changes of VEGF in serum incubated A549 cells treated with Zoledronic acid by using western blot analysis. Equal amounts of protein were loaded in each lane. β‐actin was used as internal control. (c) Zol reduced VEGF secretion in culture medium.
See this image and copyright information in PMC

References

    1. Yuasa T, Kimura S, Ashihara E, Habuchi T, Maekawa T (2007) Zoledronic acid – a multiplicity of anti‐cancer action. Curr. Med. Chem. 14, 2126–2135. - PubMed
    1. Wood J, Bonjean K, Ruetz S, Bellahcène A, Devy L, Foidart JM et al. (2002) Novel antiangiogenic effects of the bisphosphonate compound zoledronic acid. J. Pharmacol. Exp. Ther. 302, 1055–1061. - PubMed
    1. Santini D, Vincenzi B, Avvisati G, Dicuonzo G, Battistoni F, Gavasci M et al. (2002) Pamidronate induces modifications of circulating angiogenetic factors in cancer patients. Clin. Cancer Res. 8, 1080–1084. - PubMed
    1. Miller K, Wang M, Gralow J, Dickler M, Cobleigh M, Perez EA et al. (2007) Paclitaxel plus bevacizumab versus paclitaxel alone for metastatic breast cancer. N. Eng. J. Med. 357, 2666–2676. - PubMed
    1. Ramalingam SS et al. (2008) Outcomes for elderly, advanced‐stage non‐small‐cell lung cancer patients treated with bevacizumab in combination with carboplatin and paclitaxel: analysis of Eastern Cooperative Oncology Group Trial 4599. J. Clin. Oncol. 26, 60. - PubMed

MeSH terms