Pentoxifylline potentiates the antitumor effect of cisplatin and etoposide on human lung cancer cell lines.
The effect of pentoxifylline (PENT) on the sensitivity of two human lung adenocarcinoma cell lines, PC-9 and PC-14, to cisplatin (CDDP) and etoposide (ET) was studied. PENT at 0.5 and 1 mM enhanced the cytotoxicity of CDDP and ET on PC-14 and PC-9, respectively. Isobologram analyses of IC50 data, as well as combination index calculations, revealed that PENT had an additive or a synergistic effect when applied in combination with CDDP or ET, respectively. PENT potentiated the antitumor effect of ET in a nude-mouse xenograft model using PC-14 cells, when PENT was administered at 150 mg/kg subcutaneously for 6 days. Flow cytometry revealed that PENT decreased the accumulation of cells in the G2+M phase caused by CDDP when using PC-9 cells. However, PENT did not remarkably alter the accumulation of cells in G2+M caused by ET. These results suggest that PENT enhanced the antitumor effects of CDDP additively and those of ET synergistically. The enhancement mechanism probably differs between CDDP and ET. PENT needs more study to elucidate its potency as a new agent for combination chemotherapy.
Ohsaki
Y
Y
First Department of Medicine, Asahikawa Medical College, Japan.
Ishida
S
S
Fujikane
T
T
Kikuchi
K
K
D000230:Adenocarcinoma / Q000188:drug therapy* / Q000473:pathology; D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use / Q000633:toxicity*; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D002945:Cisplatin / Q000627:therapeutic use / Q000633:toxicity*; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D005047:Etoposide / Q000627:therapeutic use / Q000633:toxicity*; D005434:Flow Cytometry; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000473:pathology; D008297:Male; D051379:Mice; D008819:Mice, Nude; D010431:Pentoxifylline / Q000627:therapeutic use / Q000633:toxicity*; D014183:Transplantation, Heterologous; D014407:Tumor Cells, Cultured; D014410:Tumor Stem Cell Assay
D000970:Antineoplastic Agents; D005047:Etoposide; D002945:Cisplatin; D010431:Pentoxifylline