Enhanced tumor cures after Foscan photodynamic therapy combined with the ceramide analog LCL29. Evidence from mouse squamous cell carcinomas for sphingolipids as biomarkers of treatment response

  • Authors:
    • D. Separovic
    • J. Bielawski
    • J. S. Pierce
    • S. Merchant
    • A. L. Tarca
    • G. Bhatti
    • B. Ogretmen
    • M. Korbelik
  • View Affiliations

  • Published online on: December 6, 2010     https://doi.org/10.3892/ijo.2010.863
  • Pages: 521-527
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Abstract

To improve anticancer therapeutic success of photodynamic therapy (PDT), combination treatments represent a viable strategy. Sphingolipid analogs combined with anticancer drugs can enhance tumor response. We have shown that LCL29, a C6-pyridinium ceramide, promotes therapeutic efficacy of Photofrin-PDT in mouse SCCVII squamous cell carcinoma tumors. The long-term effect of the combination PDT + LCL29 is unknown. In this study we used the same model to test the long-term curative potential of Foscan-PDT + LCL29. We show that treatment of SCCVII tumors with the combination led to enhanced long-term tumor cure compared to PDT alone. LCL29 itself did not prevent tumor growth. All treatments triggered early increases in tumor-associated C16-ceramide, C18-ceramide, dihydrosphingosine, and global levels of dihydroceramides. PDT-evoked increases in tumor-associated sphingosine-1-phosphate and dihydrosphingosine-1-phosphate remained elevated or were attenuated after the combination, respectively; in contrast, LCL29 had no effect on these two sphingolipids. Our data demonstrate that adjuvant LCL29 improves PDT long-term therapeutic efficacy, implying translational potential of the combination. Furthermore, our findings indicate that changes in the sphingolipid profile might serve as predictive biomarkers of tumor response to treatments.

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February 2011
Volume 38 Issue 2

Print ISSN: 1019-6439
Online ISSN:1791-2423

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Spandidos Publications style
Separovic D, Bielawski J, Pierce JS, Merchant S, Tarca AL, Bhatti G, Ogretmen B and Korbelik M: Enhanced tumor cures after Foscan photodynamic therapy combined with the ceramide analog LCL29. Evidence from mouse squamous cell carcinomas for sphingolipids as biomarkers of treatment response. Int J Oncol 38: 521-527, 2011
APA
Separovic, D., Bielawski, J., Pierce, J.S., Merchant, S., Tarca, A.L., Bhatti, G. ... Korbelik, M. (2011). Enhanced tumor cures after Foscan photodynamic therapy combined with the ceramide analog LCL29. Evidence from mouse squamous cell carcinomas for sphingolipids as biomarkers of treatment response. International Journal of Oncology, 38, 521-527. https://doi.org/10.3892/ijo.2010.863
MLA
Separovic, D., Bielawski, J., Pierce, J. S., Merchant, S., Tarca, A. L., Bhatti, G., Ogretmen, B., Korbelik, M."Enhanced tumor cures after Foscan photodynamic therapy combined with the ceramide analog LCL29. Evidence from mouse squamous cell carcinomas for sphingolipids as biomarkers of treatment response". International Journal of Oncology 38.2 (2011): 521-527.
Chicago
Separovic, D., Bielawski, J., Pierce, J. S., Merchant, S., Tarca, A. L., Bhatti, G., Ogretmen, B., Korbelik, M."Enhanced tumor cures after Foscan photodynamic therapy combined with the ceramide analog LCL29. Evidence from mouse squamous cell carcinomas for sphingolipids as biomarkers of treatment response". International Journal of Oncology 38, no. 2 (2011): 521-527. https://doi.org/10.3892/ijo.2010.863