Lasers in Medical Science

, Volume 33, Issue 6, pp 1215–1223 | Cite as

High doses of laser phototherapy can increase proliferation in melanoma stromal connective tissue

  • Lúcio Frigo
  • Joseli Maria Cordeiro
  • Giovani Marino Favero
  • Durnavei Augusto Maria
  • Ernesto Cesar Pinto Leal-Junior
  • Jon Joensen
  • Jan Magnus Bjordal
  • Denise Carvalho Roxo
  • Rodrigo Labat Marcos
  • Rodrigo Alvaro Brandão Lopes-Martins
Original Article


It is well established that laser phototherapy (LP) is contraindicated directly over cancer cells, due to its bio modulatory effects in cell and blood vessel proliferation. The aim of the present study was to analyze the influence of typical low-level laser therapy (LLLT) and high intensity laser therapy (HILT) and an in-between dose of 9 J on collagen fibers and blood vessels content in melanoma tumors (B16F10) implanted in mice. Melanoma tumor cells were injected in male Balb C mice which were distributed in four groups: control (no irradiated) or irradiated by 3, 9, or 21 J (150; 450, or 1050 J/cm2). LP was performed in daily sessions for 3 days with a InGaAlP—660 nm (mean output: 50 mW, spot size: 2 mm2). Tumor volume was analyzed using (1) picrosirius staining to quantify collagen fibers content and (2) Verhoeff’s method to quantify blood vessels content. Tumor growth outcome measured in the 3-J group was not significantly different from controls. Nine and 21-J groups, presented significant and dose-dependent increases in tumor volume. Quantitative analysis of the intensity of collagen fibers and their organization in stroma and peri-tumoral microenvironment showed significant differences between irradiated and control group. Blood vessels count of 21-J group outnumbered the other groups. High doses (≥ 9 J) of LP showed a dose-dependent tumor growth, different collagen fibers characteristics, and eventually blood vessel growth, while a typical LLLT dose (3 J) appeared harmless on melanoma cell activity.


Photobiomodulation LLLT Melanoma Collagen Bloob vessels Growing tumor 


Funding information

Professor Lucio Frigo is thankful for the financial support of FAPESP (2007/59124-0).

Compliance with ethical standards

Ethical commit

All experiments were carried out in accordance with the guidelines from Cruzeiro do Sul University Bioethical Council for human and animal care, PROTOCOL 011/07.

Conflict of interest

The authors declare that they have no conflict of interest.


Professor Ernesto Cesar Pinto Leal-Junior received research support from Multi Radiance Medical (Solon, OH), a laser device manufacturer.

Informed consent

All authors agree to the submission of this manuscript.


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Copyright information

© Springer-Verlag London Ltd., part of Springer Nature 2018

Authors and Affiliations

  • Lúcio Frigo
    • 1
  • Joseli Maria Cordeiro
    • 1
  • Giovani Marino Favero
    • 2
  • Durnavei Augusto Maria
    • 3
  • Ernesto Cesar Pinto Leal-Junior
    • 4
  • Jon Joensen
    • 5
  • Jan Magnus Bjordal
    • 5
    • 6
  • Denise Carvalho Roxo
    • 1
  • Rodrigo Labat Marcos
    • 4
    • 7
  • Rodrigo Alvaro Brandão Lopes-Martins
    • 8
  1. 1.Biological Sciences and Health CenterCruzeiro do Sul UniversitySão PauloBrazil
  2. 2.General Biology DepartmentState University of Ponta GrossaPonta GrossaBrazil
  3. 3.Laboratory of Biochemistry and BiophysicsButantan InstituteSão PauloBrazil
  4. 4.Nove de Julho University (UNINOVE)São PauloBrazil
  5. 5.Institute for PhysiotherapyBergen University CollegeBergenNorway
  6. 6.Physiotherapy Research Group, Department of Global and Public HealthUniversity of BergenBergenNorway
  7. 7.Biophotonics Applied in Health SciencesUniversidade Nove de JulhoSão PauloBrazil
  8. 8.Universidade do Vale do ParaíbaSão José dos CamposBrazil

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