Preclinical Efficacy Testing for Stomach and Liver Cancers
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PurposeHollow fiber assays offer an early in vivo method of anticancer drug screening. Theassays have been optimized for human cancers originating from the lung, breast,colon, ovary, and brain, but not from the stomach and liver. The current study focusedon optimization of hollow fiber assays for gastric and hepatocellular carcinoma celllines. Materials and MethodsGastric (SNU-16, SNU-484, SNU-668) and hepatocellular (HepG2, SK-Hep-1, Hep3B)carcinoma cell lines in hollow fibers were transplanted subcutaneously and intraperitoneallyinto mice, which were subsequently treated with a standard anticancer agent,paclitaxel. The hollow fiber activity of paclitaxel in each cell line was compared withthe xenograft activity. ResultsUsing optimized inoculation densities and schedules, treatment with paclitaxel waseffective in gastric carcinoma cell lines, SNU-16 and SNU-484, but not in SNU-668. In the hollow fiber assays, paclitaxel was effective in hepatocellular carcinoma celllines, HepG2 and SK-Hep-1, but not in Hep3B. Consistent with the results of thehollow fiber assay, SNU-16 and SNU-484, but not SNU-668, showed tumor regression,and HepG2 and SK-Hep-1, but not Hep3B, showed effective tumor responses followingtreatment with paclitaxel in xenograft models. When EW7197, a novel compound,and flavopiridol were tested in SNU-16 cells under optimized conditions, the hollowfiber activity showed good correlation with the xenograft activity of each compound. ConclusionOur protocols may be useful for screening candidate small molecules that may exhibitactivity against stomach and liver cancers, both of which are common in Korea.
Abstract
PurposeHollow fiber assays offer an early in vivo method of anticancer drug screening. Theassays have been optimized for human cancers originating from the lung, breast,colon, ovary, and brain, but not from the stomach and liver. The current study focusedon optimization of hollow fiber assays for gastric and hepatocellular carcinoma celllines. Materials and MethodsGastric (SNU-16, SNU-484, SNU-668) and hepatocellular (HepG2, SK-Hep-1, Hep3B)carcinoma cell lines in hollow fibers were transplanted subcutaneously and intraperitoneallyinto mice, which were subsequently treated with a standard anticancer agent,paclitaxel. The hollow fiber activity of paclitaxel in each cell line was compared withthe xenograft activity. ResultsUsing optimized inoculation densities and schedules, treatment with paclitaxel waseffective in gastric carcinoma cell lines, SNU-16 and SNU-484, but not in SNU-668. In the hollow fiber assays, paclitaxel was effective in hepatocellular carcinoma celllines, HepG2 and SK-Hep-1, but not in Hep3B. Consistent with the results of thehollow fiber assay, SNU-16 and SNU-484, but not SNU-668, showed tumor regression,and HepG2 and SK-Hep-1, but not Hep3B, showed effective tumor responses followingtreatment with paclitaxel in xenograft models. When EW7197, a novel compound,and flavopiridol were tested in SNU-16 cells under optimized conditions, the hollowfiber activity showed good correlation with the xenograft activity of each compound. ConclusionOur protocols may be useful for screening candidate small molecules that may exhibitactivity against stomach and liver cancers, both of which are common in Korea.
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