Zoledronic acid as an antimetastatic agent for different human tumor cell lines
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Laura Muinelo-Romay1, Daniel Garcia, Lorena Alonso-Alconada
1Translational Medical Oncology; Health Research Institute of Santiago (IDIS); SERGAS; Santiago de Compostela, Spain. rafael.lopez.lopez@sergas.es.
Background:
Zoledronic acid effectively reduces skeletal events in patients with metastatic disease. The results of pre-clinical and emerging clinical data suggest an additional activity of zoledronic acid as an antitumor agent, interfering with the growth and dissemination of malignant cells. However, the mechanisms by which zoledronic acid impairs tumor progression are practically unknown. In the present study, we aimed to investigate the impact of zoledronic acid on invasion and colony formation ability of different human tumour cell lines.
Materials And Methods:
Human ovarian (SKOV3), colonic (HCT116), endometrial (HEC1A and Ishikawa) and breast cancer (MCF-7, MDA-MB-231, HCC1937, SKBR3 and T47D) cell lines were treated with different concentrations (10-100 μM) of zoledronic acid and analyzed using 3D assays to test their invasiveness and their ability to grow anchorage-independently, both hallmarks of aggressive tumor cell behavior.
Results:
The most intense effect of the drug on tumor invasion was observed on MDA-MB-231 cells, but at high concentrations HEC1A, SKOV3 and SKBR3 cells also exhibited reduced invasion capacity. We also found a significant reduction of colony formation under zoledronic acid treatment in MCF-7, T47-D, HCT116, Ishikawa, HEC1A and SKOV3 cells.
Conclusion:
Zoledronic acid presents an interesting potential for use as anti-metastatic agent for different solid tumor types, affecting relevant steps of tumor dissemination.
Insights
Zoledronic acid, known for reducing skeletal events, also inhibits tumor cell invasion and colony formation in various cancer types. This suggests its potential as an anti-metastatic agent for solid tumors.
Area of Science:
- Oncology
- Pharmacology
- Cancer Biology
Background:
- Zoledronic acid is established for reducing skeletal events in metastatic cancer.
- Pre-clinical and emerging data suggest zoledronic acid possesses antitumor properties.
- Mechanisms of zoledronic acid's anti-tumor effects, particularly on tumor progression, remain largely unknown.
Purpose of the Study:
- To investigate the impact of zoledronic acid on the invasion and colony formation abilities of human tumor cell lines.
- To explore zoledronic acid's potential as an anti-metastatic agent.
Main Methods:
- Multiple human cancer cell lines (ovarian, colonic, endometrial, breast) were treated with zoledronic acid (10-100 μM).
- 3D assays were employed to assess tumor cell invasiveness.
- Colony formation assays evaluated anchorage-independent growth, a hallmark of aggressive tumors.
Main Results:
- Zoledronic acid significantly reduced tumor cell invasion in MDA-MB-231, HEC1A, SKOV3, and SKBR3 cell lines.
- A significant reduction in colony formation was observed in MCF-7, T47-D, HCT116, Ishikawa, HEC1A, and SKOV3 cells upon zoledronic acid treatment.
Conclusions:
- Zoledronic acid demonstrates potential as an anti-metastatic agent for various solid tumors.
- The drug affects critical steps in tumor cell dissemination, including invasion and colony formation.
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