Zoledronic acid and irradiation in oral squamous cell carcinoma.

OBJECTIVE This in vitro study evaluated cytotoxicity and cell migration effects of zoledronic acid and irradiation upon oral squamous cell carcinoma. MATERIALS AND METHODS Zoledronic acid was administrated at doses of 10, 25, 50, and 100 μM to PE/CA-PJ15 oral squamous cell carcinoma cultures, irradiated with different doses (0, 5, 15, and 30 Gy), followed by evaluation of the effects on cell viability. Cell migration capacity was studied after 24- and 72-h incubation. RESULTS At 24 h, the 100 μM concentration of zoledronic acid combined with 15 Gy irradiation caused the greatest decrease in cell viability. At 72 h, statistically significant decreases in cell viability were found with all concentrations of zoledronic acid with or without irradiation: 0 Gy (P < 0.001), 5 Gy (P < 0.001), 15 Gy (P < 0.001), and 30 Gy (P < 0.001). 50 μM and 100 μM doses of zoledronic acid combined with 5 Gy irradiation yielded the greatest decrease in cell migration capacity. CONCLUSIONS Zoledronic acid increases cytotoxic activity in the PE/CA-PJ15 cell line and reduces cell migration capacity. These findings suggest that combination therapy using biphosphates and radiation may offer a promising therapy.

[1]  K. Kihara,et al.  Zoledronic Acid Sensitizes Renal Cell Carcinoma Cells to Radiation by Downregulating STAT1 , 2013, PloS one.

[2]  M. Alcaraz,et al.  Zoledronic acid and radiation: toxicity, synergy or radiosensitization? , 2013, Clinical and Translational Oncology.

[3]  W. Koch,et al.  Evidence-based clinical recommendations regarding screening for oral squamous cell carcinomas , 2010, BDJ.

[4]  J. Califano,et al.  Global Oral Health Inequalities in Incidence and Outcomes for Oral Cancer , 2011, Advances in dental research.

[5]  Hisao Ito,et al.  Zoledronic acid, a third-generation bisphosphonate, inhibits cellular growth and induces apoptosis in oral carcinoma cell lines. , 2011, Oncology reports.

[6]  G. Morgan,et al.  Antitumor effects and anticancer applications of bisphosphonates. , 2010, Seminars in oncology.

[7]  T. Kubo,et al.  Combined effects of bisphosphonate and radiation on osteosarcoma cells. , 2010, Anticancer research.

[8]  R. Berardi,et al.  Can we consider zoledronic acid a new antitumor agent? Recent evidence in clinical setting. , 2010, Current cancer drug targets.

[9]  R. Martínez-Monge,et al.  Concomitant Cisplatin, Paclitaxel, and Hyperfractionated Radiotherapy in Locally Advanced Head and Neck Cancer: Comparison of Two Different Schedules , 2009, American journal of clinical oncology.

[10]  S. Doggrell.  Clinical efficacy and safety of zoledronic acid in prostate and breast cancer , 2009, Expert review of anticancer therapy.

[11]  C. Scully,et al.  Oral squamous cell carcinoma: overview of current understanding of aetiopathogenesis and clinical implications. , 2009, Oral diseases.

[12]  A. Romani,et al.  Zoledronic acid determines S-phase arrest but fails to induce apoptosis in cholangiocarcinoma cells. , 2009, Biochemical pharmacology.

[13]  S. Warnakulasuriya.  Global epidemiology of oral and oropharyngeal cancer. , 2009, Oral oncology.

[14]  T. Kijima,et al.  Radiotherapy to bone metastases from renal cell carcinoma with or without zoledronate , 2009, BJU international.

[15]  V. Vassiliou,et al.  The management of metastatic bone disease with the combination of bisphosphonates and radiotherapy: from theory to clinical practice. , 2009, Anti-cancer agents in medicinal chemistry.

[16]  A. Schweitzer,et al.  Biodistribution and Plasma Protein Binding of Zoledronic Acid , 2008, Drug Metabolism and Disposition.

[17]  Dong M Shin,et al.  Recent advances in head and neck cancer. , 2008, The New England journal of medicine.

[18]  D. Amadori,et al.  Zoledronic acid increases docetaxel cytotoxicity through pMEK and Mcl-1 inhibition in a hormone-sensitive prostate carcinoma cell line , 2008, Journal of Translational Medicine.

[19]  T. Guise.  Antitumor effects of bisphosphonates: promising preclinical evidence. , 2008, Cancer treatment reviews.

[20]  O. Ozturk,et al.  Cisplatin cytotoxicity is enhanced with zoledronic acid in A549 lung cancer cell line: Preliminary results of an in vitro study , 2007, Cell biology international.

[21]  T. Kubo,et al.  Combined effects of a third-generation bisphosphonate, zoledronic acid with other anticancer agents against murine osteosarcoma , 2007, British Journal of Cancer.

[22]  T. Krieg,et al.  Morphometric analysis of murine skin wound healing: Standardization of experimental procedures and impact of an advanced multitissue array technique , 2007, Wound repair and regeneration : official publication of the Wound Healing Society [and] the European Tissue Repair Society.

[23]  M. Ozcan,et al.  In vitro synergistic cytoreductive effects of zoledronic acid and radiation on breast cancer cells , 2006, Breast Cancer Research.

[24]  R. Coleman,et al.  Role of bisphosphonates for the management of skeletal complications and bone pain from skeletal metastases. , 2006, Supportive cancer therapy.

[25]  A. Ural,et al.  Radiosensitizing effect of zoledronic acid in small cell lung cancer. , 2005, Lung cancer.

[26]  Amanda Y. Chan,et al.  Cell migration and invasion assays. , 2005, Methods.

[27]  J. Bagan,et al.  Bisphosphonates, as a new cause of drug-induced jaw osteonecrosis: an update. , 2005, Medicina oral, patologia oral y cirugia bucal.

[28]  Roger M Macklis,et al.  Synergistic cytotoxic effects of zoledronic acid and radiation in human prostate cancer and myeloma cell lines. , 2005, International journal of radiation oncology, biology, physics.

[29]  H. Wada,et al.  Efficacy of the third-generation bisphosphonate, zoledronic acid alone and combined with anti-cancer agents against small cell lung cancer cell lines. , 2005, Lung cancer.

[30]  Jonathan R. Green.  Bisphosphonates: preclinical review. , 2004, The oncologist.

[31]  M. Pandey,et al.  Mandibular invasion in oral squamous cell carcinoma: investigation by clinical examination and orthopantomogram. , 2004, International journal of oral and maxillofacial surgery.

[32]  J. Jacobs,et al.  Postoperative concurrent radiotherapy and chemotherapy for high-risk squamous-cell carcinoma of the head and neck. , 2004, The New England journal of medicine.

[33]  A. Ural,et al.  The Bisphosphonate Zoledronic Acid Induces Cytotoxicity in Human Myeloma Cell Lines with Enhancing Effects of Dexamethasone and Thalidomide , 2003, International journal of hematology.

[34]  C. Boland,et al.  Zoledronic acid induces antiproliferative and apoptotic effects in human pancreatic cancer cells in vitro , 2003, British Journal of Cancer.

[35]  T. Helliwell,et al.  Mandibular invasion in patients with oral and oropharyngeal squamous carcinoma. , 1997, Clinical otolaryngology and allied sciences.

[36]  J. Minna,et al.  Evaluation of a tetrazolium-based semiautomated colorimetric assay: assessment of radiosensitivity. , 1987, Cancer research.

[37]  James B. Mitchell,et al.  Evaluation of a tetrazolium-based semiautomated colorimetric assay: assessment of chemosensitivity testing. , 1987, Cancer research.