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 β1 (TGFβ1). T.T., MKN28, and MKN45 cell lines were treated with TGFβ1 before exposure to ADM. Athymic female mice bearing the MKN28 cells were treated with TGFβ1, ADM, or TGFβ1+ADM. Pretreatment of T.T., MKN28, and MKN45 cell lines with TGFβ1 resulted in increased sensitivity to ADM. In contrast, simultaneous exposure to TNFα, which increased MnSOD expression, decreased sensitivity of cancer cells to ADM. In vivo studies demonstrated that the combined administration of TGFβ1 and ADM delayed tumor growth better than either treatment alone. Our results suggest that the synergistic antitumor effects of TGFβ1 and ADM may be due to decreased MnSOD expression in cancer cells. Thus, combined administration of TGFβ1 and ADM might prove useful for treatment of malignant disease.