Potentiation of the Antiumor Effects of Cisplatin and Etoposide by Pentoxifylline in Human Lung Cancer Cell Lines.
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The effects of pentoxifylline on human lung adenocarcinoma cells (PC-9, PC-14) treated with cisplatin or etoposide were studied.<BR>Cytotoxic effects of cisplatin and etoposide were potentiated against these cells in culture. Isobologram analysis of IC<SUB>50</SUB> revealed pentoxifylline to show additive or supra -additive effects in combination with cisplatin or etoposide, respectively. In a nude mouse xenograft model of PC-14, the potentiation of antitumor effects of etoposide was observed in the combination treatment with pentoxifylline. From these results, pentoxifylline might enable a new combination modality of cancer chemotherapy.<BR>In cell cycle analysis of PC-9, DNA histogram by flowcytometry indicated pentoxifylline to course a decrease in cell storage of cisplatin and etoposide in the G2 phase. Moreover, the DNA/BrdU analysis revealed that pentoxifylline inhibited the delay due to etoposide in the G2 phase passage. It is thought that the potentiation of the cytotoxic effect of cisplatin and etoposide by pentoxifylline is related to the inhibitory action of G., delay in addition to DNA repair inhibitory action.
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