Cisplatin induces fas expression in esophageal cancer cell lines and enhanced cytotoxicity in combination with LAK cells.

OBJECTIVE: To establish a new therapeutic approach for the treatment of esophageal cancer, we investigated an alternative mechanism of immunotherapy for sensitizing target cells to effector cells.
METHODS: Six human esophageal cancer cell lines were used. The expression of Fas antigen on tumor cells was determined by flow cytometry. The cytotoxic effect of cis-dichlorodiammineplatinum (CDDP) and anti-Fas antibody was evaluated using an MTT assay. The cytotoxic activity of LAK cells was measured by a (51)Cr release assay.
RESULTS: Five out of six esophageal cancer cell lines expressed Fas antigen at various levels (26.2-61.5%), and Fas expression increased after CDDP treatment. The antitumor effect of anti-Fas antibody on the esophageal cancer cell line and the antitumor effect of LAK cells activated by IL-2 were enhanced by pretreatment with CDDP. After concanamycin A treatment to specifically evaluate Fas-dependent cytotoxicity, LAK cells expressing Fas ligand killed only Fas-positive cells, but not Fas-negative cells. An anti-Fas neutralizing antibody inhibited this cytotoxicity. DNA fragmentation was shown in a cell line that was treated with CDDP and anti-Fas antibody, and also in the targeted esophageal cancer cell line cocultured with LAK cells.
CONCLUSION: Our results suggest a potential clinical application of CDDP as a Fas inducer to make esophageal tumors susceptible to Fas antigen and LAK cytotoxicity. Copyright 2000 S. Karger AG, Basel.