Expression of manganese superoxide disumutase influences chemosensitivity in esophageal and gastric cancers.
The purpose of this study was to examine whether the increased sensitivity of cancer cells to adriamycin (ADM), which is known to produce superoxide radicals, was brought through suppressed manganese superoxide disumutase (MnSOD) expression in the presence of transforming growth factor beta1 (TGFbeta1). T.T., MKN28, and MKN45 cell lines were treated with TGFbeta1 before exposure to ADM. Athymic female mice bearing the MKN28 cells were treated with TGFbeta1, ADM, or TGFbeta1 + ADM. Pretreatment of T.T., MKN28, and MKN45 cell lines with TGFbeta1 resulted in increased sensitivity to ADM. In contrast, simultaneous exposure to TNFalpha, which increased MnSOD expression, decreased sensitivity of cancer cells to ADM. In vivo studies demonstrated that the combined administration of TGFbeta1 and ADM delayed tumor growth better than either treatment alone. Our results suggest that the synergistic antitumor effects of TGFbeta1 and ADM may be due to decreased MnSOD expression in cancer cells. Thus, combined administration of TGFbeta1 and ADM might prove useful for treatment of malignant disease.
Izutani
Ryo
R
Department of Surgery II, Kinki University School of Medicine, Osaka-Sayama, Osaka, Japan. geka-2@med.kindai.ac.jp
Kato
Michio
M
Asano
Satoshi
S
Imano
Motohiro
M
Ohyanagi
Harumasa
H
D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D003196:Computer Graphics; D004195:Disease Models, Animal; D004317:Doxorubicin / Q000627:therapeutic use*; D004938:Esophageal Neoplasms / Q000188:drug therapy* / Q000201:enzymology*; D005260:Female; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D009363:Neoplasm Proteins / Q000378:metabolism*; D018709:Statistics, Nonparametric; D013274:Stomach Neoplasms / Q000188:drug therapy* / Q000201:enzymology*; D013482:Superoxide Dismutase / Q000378:metabolism*; D016212:Transforming Growth Factor beta / Q000627:therapeutic use; D053773:Transforming Growth Factor beta1; D014407:Tumor Cells, Cultured / Q000187:drug effects; D014409:Tumor Necrosis Factor-alpha / Q000627:therapeutic use
D000970:Antineoplastic Agents; D009363:Neoplasm Proteins; C508960:TGFB1 protein, human; C508961:Tgfb1 protein, mouse; D016212:Transforming Growth Factor beta; D053773:Transforming Growth Factor beta1; D014409:Tumor Necrosis Factor-alpha; D004317:Doxorubicin; D013482:Superoxide Dismutase