Photobiomodulation effects on head and neck squamous cell carcinoma (HNSCC) in an orthotopic animal model

  • Andrei BaraschEmail author
  • Hongyan Li
  • Vinagolu K. Rajasekhar
  • Judith Raber-Durlacher
  • Joel B. Epstein
  • James Carroll
  • Adriana Haimovitz-Friedman
Original Article



Photobiomodulation (PBM) has shown efficacy in preventing and treating cancer therapy-induced mucositis and dermatitis. However, there is contradictory information regarding the effect of PBM on (pre)malignant cells, which has led to questions regarding the safety of this technique. We address this issue using an orthotopic mouse model (Cal-33) with human squamous cell carcinoma of the oral cavity.


Mice with actively growing orthotopic Cal-33 head and neck carcinoma tumors were divided into 4 groups: control, PBM only, radiation therapy (RT) only, and PBM + RT. We performed three experiments: (1) PBM at 660 nm, 18.4 J/cm2, and 5 RT × 4 Gy doses delivered daily; (2) PBM at 660 nm, 18.4 J/cm2, and 1 × 15 Gy RT; and (3) PBM at 660 nm + 850 nm, 45 mW/cm2, 3.4 J/cm2, and 1 × 15 Gy RT. Mice were weighed daily and tumor volumes were evaluated by IVIS. Survival time was also evaluated.


Animals treated with RT survived significantly longer and had significantly smaller tumor volume when compared with the control and PBM-only treatment groups. No significant differences were noted between the RT alone and PBM + RT groups in any of the experiments.


Our results suggest that PBM at the utilized parameters does not provide protection to the tumor from the killing effects of RT.


Photobiomodulation Radiation therapy Head and neck cancer Orthotopic mouse model 



We thank the following core facilities at MSKCC: Molecular Cytology and Small Animal Imaging.

Funding information

This work was supported in part by the Department of Radiation Oncology and the Cancer Center Support Grant (P30 CA008748), the NIH.

Compliance with ethical standards

Conflict of interest

James Carrol is the CEO of Thor Laser. None of the other authors declare any conflict of interest.


  1. 1.
    Barasch A, Peterson D (2003) Risk factors for ulcerative oral mucositis in cancer patients: unanswered questions. Oral Oncol 39:91–100CrossRefGoogle Scholar
  2. 2.
    Al-Dasooqi N, Sonis ST, Bowen JM, Bateman E et al (2013) Emerging evidence on the pathobiology of mucositis. Support Care Cancer 21:2075–2083CrossRefGoogle Scholar
  3. 3.
    Holanda de Mendonca RM, de Araujo M, Levy CE et al (2012) Prospective evaluation of HSV, Candida spp., and oral bacteria on the severity of oral mucositis in pediatric acute lymphoblastic leukemias. Support Care Cancer 20:1101–1107CrossRefGoogle Scholar
  4. 4.
    Barasch A, Coke MJ (2007) Cancer therapeutics: an update on its effects on oral health. Periodontology 2000 44:44–54CrossRefGoogle Scholar
  5. 5.
    Peterson DE, Ohrn K, Bowen J et al (2013) Systematic review of oral cryotherapy for management of oral mucositis caused by cancer therapy. Support Care Cancer 21:327–332CrossRefGoogle Scholar
  6. 6.
    Barasch A, Epstein J, Tilashalski K (2009) Palifermin for management of treatment-induced oral mucositis in cancer patients. Biologics 3:111–116PubMedPubMedCentralGoogle Scholar
  7. 7.
    Lalla RV, Bowen J, Barasch A, Elting L, Epstein J, Keefe DM, McGuire DB, Migliorati C, Nicolatou-Galitis O, Peterson DE, Raber-Durlacher JE, Sonis ST, Elad S, The Mucositis Guidelines Leadership Group of the Multinational Association of Supportive Care in Cancer and International Society of Oral Oncology (MASCC/ISOO) (2014) MASCC/ISOO clinical practice guidelines for the management of mucositis secondary to cancer therapy. Cancer 120:1453–1461CrossRefGoogle Scholar
  8. 8.
    Bjordal JM, Bensadoun RJ, Tuner J et al (2011) A systematic review with meta-analysis of the effect of low-level laser therapy (LLLT) in cancer therapy-induced oral mucositis. Support Care Cancer 19:1069–1077CrossRefGoogle Scholar
  9. 9.
    Clarkson JE, Worthington HV, Furness S et al (2010) Interventions for treating mucositis for patients with cancer receiving treatment. Cochrane Database Syst Rev 8:CD001973Google Scholar
  10. 10.
    Migliorati C, Hewson I, Lalla RV, Antunes HS et al (2013) Systematic review of laser and other light therapy for the management of oral mucositis in cancer patients. Support Care Cancer 21:333–341CrossRefGoogle Scholar
  11. 11.
    Oberoi S, Zamperlini-Netto G, Beyene J, Treister NS, Sung L (2014) Effect of prophylactic low level laser therapy on oral mucositis: a systematic review and meta-analysis. PLoS One 9:e107418CrossRefGoogle Scholar
  12. 12.
    Rhee YH, Moon JH, Choi SH, Ahn JC (2016) Low-level laser therapy promoted aggressive proliferation and angiogenesis through decreasing of transforming growth factor-b1 and increasing of Akt/Hypoxia inducible factor -1a in anaplastic thyroid cancer. Photomed Laser Surg 34:229–235CrossRefGoogle Scholar
  13. 13.
    Sperandio FF, Giudice FS, Correa L, Pinto DS et al (2013) Low-level laser therapy can produce increased aggressiveness of dysplastic and oral cancer cell lines by modulation of Akt/mTOR signaling pathway. J Biophotonics 6:839–847PubMedPubMedCentralGoogle Scholar
  14. 14.
    Barasch A, Raber-Durlacher JE, Epstein JB, Carroll J (2016) Effects of pre-radiation exposure to LLLT of normal and malignant cells. Supp Care Cancer 24:2497–2501CrossRefGoogle Scholar
  15. 15.
    Djavid GE, Bigdeli B, Goliaei B, Nikoofar A, Hamblin MR (2017) Photobiomodulation leads to enhanced radiosensitivity through induction of apoptosis and autophagy in human cervical cancer cells. J Biophotonics 10:1732–1742. CrossRefPubMedPubMedCentralGoogle Scholar
  16. 16.
    Liang WZ, Liu PF, FU E, Chung HS et al (2015) Selective cytotoxic effects of low-power laser irradiation on human oral cancer cells. Lasers Surg Med 47:756–764CrossRefGoogle Scholar
  17. 17.
    Antunes HS, Herchenhorn D, Small IA, Araújo CMM, Viégas CMP, de Assis Ramos G, Dias FL, Ferreira CG (2017) Long-term survival of a randomized phase III trial of head and neck cancer patients receiving concurrent chemoradiation therapy with or without low-level laser therapy (LLLT) to prevent oral mucositis. Oral Oncol 71:11–15CrossRefGoogle Scholar
  18. 18.
    Mizrachi A, Vinagolu RK, Brook S, Ghossein R, Haimovitz Friedman A (2018) A novel orthotopic oral squamous cell carcinoma animal model for preclinical studies of different treatment modalities. JAMA (abstr)Google Scholar
  19. 19.
    Ottaviani G, Martinelli V, Rupel K, Caronni N, Naseem A, Zandonà L, Perinetti G, Gobbo M, di Lenarda R, Bussani R, Benvenuti F, Giacca M, Biasotto M, Zacchigna S (2016) Laser therapy inhibits tumor growth in mice by promoting immune surveillance and vessel normalization. EBioMedicine 11:165–172. CrossRefPubMedPubMedCentralGoogle Scholar
  20. 20.
    Ramos Silva C, Cabral FV, de Camargo CF et al (2016) Exploring the effects of low-level laser therapy on fibroblasts and tumor cells following gamma radiation exposure. J Biophotonics 9:1157–1166CrossRefGoogle Scholar
  21. 21.
    Liu YH, Cheng CC, Ho CC et al (2004) Effects of diode 808 nm GaAlAs low-power laser irradiation on inhibition of the proliferation of human hepatoma cells in vitro and their possible mechanism. Res Commun Mol Pathol Pharmacol 115:185–201PubMedGoogle Scholar
  22. 22.
    Schartinger VH, Galvan O, Riechelmann H, Dudas J (2012) Differential response of fibroblasts, non-neoplastic epithelial cells, and oral carcinoma cells to low-level laser therapy. Support Care Cancer 20:523–529CrossRefGoogle Scholar
  23. 23.
    Zacchigna S, Gobbo M, Rupel K et al (2015) Is laser biostimulation safe even when performed in neoplastic fields? J Clin Oncol 33(suppl):3Google Scholar
  24. 24.
    Myakishev-Rempel M, Stadler I, Brondon P, Axe DR, Friedman M, Nardia FB, Lanzafame R (2012) Preliminary study of the safety of red light phototherapy of tissues harboring cancer. Photomed Laser Surg 30:551–558CrossRefGoogle Scholar
  25. 25.
    Gomes Henriques AC, Ginani F, Oliveira RM et al (2014) Low-level laser therapy promotes proliferation and invasion of oral squamous carcinoma cells. Lasers Med Sci 29:1385–1395PubMedGoogle Scholar

Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2019

Authors and Affiliations

  1. 1.Department of MedicineWeil Cornell Medical CollegeNew YorkUSA
  2. 2.Memorial Sloan Kettering Cancer CenterNew YorkUSA
  3. 3.Academic Centre for Dentistry AmsterdamUniversity of Amsterdam and VU University, and University Medical Centers, location AMCAmsterdamThe Netherlands
  4. 4.Cedars-Sinai Health System, Los Angeles and City of Hope Cancer CenterDuarteUSA
  5. 5.Thor Photomedicine LtdCheshamUK

Personalised recommendations