Journal
INTERNATIONAL JOURNAL OF ONCOLOGY
Volume 38, Issue 2, Pages 521-527Publisher
SPANDIDOS PUBL LTD
DOI: 10.3892/ijo.2010.863
Keywords
C6-pyriclinium ceramide; dihydroceramide; dihydrosphingosine; dihydrosphingosine-1-phosphate; ceramide; Foscan; photodynamic therapy; sphingolipids; sphingosine-1-phosphate; squamous cell carcinoma
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Funding
- National Cancer Institute [R01 CA77475]
- National Institute of Dental and Craniofacial Research [DE016572]
- National Center for Research Resources [C06 RR018823]
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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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