Synergistic effect of tumor necrosis factor-alpha- and diphtheria toxin-mediated cytotoxicity in sensitive and resistant human ovarian tumor cell lines.

摘要: Recent studies have demonstrated that diphtheria toxin (DTX) also mediates target cell lysis, and the mechanism of cytotoxicity has many features similar to those mediated by TNF-alpha. Thus, we hypothesized DTX TNF-alpha, used in combination, may result either additive or synergistic cytotoxic activity. This was examined on three human ovarian carcinoma lines chosen for their differing sensitivities TNF-alpha DTX, i.e., 222, which is sensitive both 222TR, a TNF-alpha-resistant DTX-sensitive variant SKOV-3, resistant The simultaneous use at suboptimal concentrations resulted activity against all tested, thus overcoming resistance 222TR double SKOV-3. DNA fragmentation observed treated with occurred as early 4 h after treatment. Cycloheximide, actinomycin D, emetine, causing greater than 90% protein synthesis inhibition, did not alone synergy suggesting due its ability inhibit synthesis. energy poisons pH conditions DTX-mediated abrogation synergy. These findings show two agents when concentrations, synergize lines. Because SKOV-3 line here chemotherapeutic drugs, combination treatment be beneficial drug resistance.