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Preclinical Efficacy Testing for Stomach and Liver Cancers

Cancer Research and Treatment 2014년 46권 2호 p.186 ~ p.193

박준원(Park Jun-Won) - Seoul National University College of Veterinary Medicine Department of Veterinary Pathology
(Baek Nam-Suk) - National OncoVenture
이석철(Lee Seok-Cheol) - National Cancer Center Biomolecular Function Research Branch
오수진(Oh Su-Jin) - National Cancer Center Biomolecular Function Research Branch
(Jang Seok-Hoon) - National Cancer Center Biomolecular Function Research Branch
김인후(Kim In-Hoo) - National Cancer Center Molecular Imaging and Therapy Branch
김대용(Kim Dae-Yong) - Seoul National University College of Veterinary Medicine
김학균(Kim Hark-Kyun) - National Cancer Center Biomolecular Function Research Branch

Abstract

Purpose: Hollow fiber assays offer an early in vivo method of anticancer drug screening. The assays 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 focused on optimization of hollow fiber assays for gastric and hepatocellular carcinoma cell lines.

Materials and Methods: Gastric (SNU-16, SNU-484, SNU-668) and hepatocellular (HepG2, SK-Hep-1, Hep3B) carcinoma cell lines in hollow fibers were transplanted subcutaneously and intraperitoneally into mice, which were subsequently treated with a standard anticancer agent, paclitaxel. The hollow fiber activity of paclitaxel in each cell line was compared with the xenograft activity.

Results: Using optimized inoculation densities and schedules, treatment with paclitaxel was effective 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 cell lines, HepG2 and SK-Hep-1, but not in Hep3B. Consistent with the results of the hollow 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 following treatment with paclitaxel in xenograft models. When EW7197, a novel compound, and flavopiridol were tested in SNU-16 cells under optimized conditions, the hollow fiber activity showed good correlation with the xenograft activity of each compound.

Conclusion: Our protocols may be useful for screening candidate small molecules that may exhibit activity against stomach and liver cancers, both of which are common in Korea.