Effects of cisplatin, interferon-alpha and 13-cis retinoic acid on the expression of Fas (CD95), intercellular adhesion molecule-1 (ICAM-1) and epidermal growth factor receptor (EGFR) in oral cancer cell lines

• Background: Previous studies showed that many chemotherapeutic agents can induce immuno-suppression at therapeutic drug concentrations whereas low drug doses induce immuno-augmentation.Methods: The effect of low-dose cisplatin, interferon-alpha, and 13-cis retinoic acid on receptors involved in immune-mediated apoptosis (Fas/CD95), cell growth (epidermal growth factor receptor) and lymphocyte adhesion (intercellular adhesion molecule-1) was investigated in two oral cancer cell lines (UT-SCC-20A and UT-SCC-24A). Different methods for cell preparation were studied: mechanical and enzymatic detachment, and culture on chamber slides. Receptor expression was investigated using immunohistochemical staining. The amount of soluble and cell-bound Fas was determined with the ELISA technique, and the functional relevance of Fas expression, apoptosis induction, was analyzed.Results: Cisplatin enhanced cytoplasm and membrane staining for Fas in both cell lines. After cisplatin treatment, the amount of soluble Fas was increased in UT-SCC-20A cultures, but no effect was observed in the UT-SCC-24A cell line. Apoptosis, measured as enhanced caspase-3 activity, was induced by an agonistic Fas antibody (CH11) after cisplatin treatment in UT-SCC-24A cells.Conclusions: Low-dose cisplatin treatment enhanced Fas expression in both cell lines and increased susceptibility to apoptosis in one of them.

Nyckelord

apoptosis

13-cis retinoic acid

cisplatin

EGFR

Fas (CD95)

ICAM-1

α-interferon

oral cancer

MEDICINE

MEDICIN

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