Cancer Res Treat.  2014 Apr;46(2):186-193.

Preclinical Efficacy Testing for Stomach and Liver Cancers

Affiliations
  • 1Biomolecular Function Research Branch, National Cancer Center, Goyang, Korea. hkim@ncc.re.kr
  • 2Department of Veterinary Pathology, College of Veterinary Medicine, Seoul National University, Seoul, Korea. daeyong@snu.ac.kr
  • 3National OncoVenture, Goyang, Korea.
  • 4Molecular Imaging and Therapy Branch, National Cancer Center, Goyang, Korea.

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.

Keyword

Hollow fiber assay; Xenograft model antitumor assay; Stomach neoplasms; Liver neoplasms

MeSH Terms

Animals
Appointments and Schedules
Brain
Breast
Carcinoma, Hepatocellular
Cell Line
Colon
Drug Evaluation, Preclinical
Female
Heterografts
Humans
Korea
Liver
Liver Neoplasms*
Lung
Mass Screening
Mice
Ovary
Paclitaxel
Stomach Neoplasms
Stomach*
Paclitaxel

Figure

  • Fig. 1 Intraperitoneal hollow fiber and xenograft activities of paclitaxel in gastric cancer cells. Error bars are presented as standard deviation.

  • Fig. 2 Intraperitoneal hollow fiber and xenograft activities of paclitaxel in hepatocellular carcinoma cells. Error bars are presented as standard deviation.

  • Fig. 3 Intraperitoneal hollow fiber and xenograft activities of EW7197 and flavopridol in SNU-16 cells. Error bar are presented as standard deviation.


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