Drug effects on CA125 antigen expression and antibody binding to cancer cells.
CA125 is a high-molecular weight glycoprotein expressed on most serous-type ovarian cancer and some lung adenocarcinoma tissues. The effects of various drugs on the release of CA125 antigen into culture medium and on monoclonal antibody (MAb) binding to cancer cells were studied using 8 human cancer cell lines, all of which expressed CA125 on their cell surfaces. The effect of dexamethasone was seen at as low a concentration as 10(-9) M dexamethasone, and the release of CA125 and the binding of radiolabelled anti-CA125 antibody were completely inhibited after exposure to 10(-7) M dexamethasone. The number of antibody binding sites markedly decreased. In contrast, sodium butyrate increased CA125 expression. These findings were clearly detected in only 3 cancer cell lines and a significant effect was not seen in the 5 other cancer cell lines. Interferon-gamma, examined in 3 cell lines, suppressed in a dose-dependent manner in 2 CA125 expression cell lines, but enhanced it in one line. No apparent effects were seen after exposure to tissue necrosis factor or interleukin-2. These results suggest that drugs may regulate the CA125 antigen expression in some, but not all, cancer cells and may affect the biodistribution of radiolabelled MAbs.
Nakai
T
T
Department of Nuclear Medicine, Kyoto University School of Medicine, Japan.
Endo
K
K
Hosono
M
M
Saga
T
T
Watanabe
Y
Y
Sakahara
H
H
Imai
K
K
Yachi
A
A
Kiyozuka
Y
Y
Ishiwata
I
I
D000911:Antibodies, Monoclonal; D015295:Antigens, Tumor-Associated, Carbohydrate / Q000032:analysis / Q000235:genetics* / Q000276:immunology; D001666:Binding Sites, Antibody / Q000187:drug effects*; D003994:Bucladesine / Q000494:pharmacology; D002087:Butyrates / Q000494:pharmacology*; D020148:Butyric Acid; D002460:Cell Line; D015179:Colorectal Neoplasms; D003907:Dexamethasone / Q000494:pharmacology*; D005260:Female; D006801:Humans; D007371:Interferon-gamma / Q000494:pharmacology*; D007376:Interleukin-2 / Q000494:pharmacology; D007700:Kinetics; D008175:Lung Neoplasms; D010051:Ovarian Neoplasms; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
D000911:Antibodies, Monoclonal; D015295:Antigens, Tumor-Associated, Carbohydrate; D002087:Butyrates; D007376:Interleukin-2; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha; D020148:Butyric Acid; D003994:Bucladesine; D003907:Dexamethasone; D007371:Interferon-gamma