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.


CONCLUSIONS
Our results suggest a potential clinical application of CDDP as a Fas inducer to make esophageal tumors susceptible to Fas antigen and LAK cytotoxicity.
Matsuzaki
I
I
Second Department of Surgery, Akita University School of Medicine, Akita City, Japan.
Suzuki
H
H
Kitamura
M
M
Minamiya
Y
Y
Kawai
H
H
Ogawa
J
J
D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis; D002945:Cisplatin / Q000494:pharmacology*; D003131:Combined Modality Therapy; D053938:DNA Fragmentation; D017931:DNA Primers; D004273:DNA, Neoplasm / Q000032:analysis; D004938:Esophageal Neoplasms / Q000188:drug therapy* / Q000378:metabolism*; D005434:Flow Cytometry; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D015979:Killer Cells, Lymphokine-Activated; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014407:Tumor Cells, Cultured; D019014:fas Receptor / Q000187:drug effects* / Q000235:genetics / Q000276:immunology
D000970:Antineoplastic Agents; D017931:DNA Primers; D004273:DNA, Neoplasm; D019014:fas Receptor; D002945:Cisplatin