Preclinical efficacy testing for stomach and liver cancers.
OBJECTIVE
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.


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.


CONCLUSIONS
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.
Biomolecular Function Research Branch, National Cancer Center, Goyang, Korea. ; Department of Veterinary Pathology, College of Veterinary Medicine, Seoul National University, Seoul, Korea.
Jun Won
JW
Park
National OncoVenture, Goyang, Korea.
Nam Suk
NS
Baek
Biomolecular Function Research Branch, National Cancer Center, Goyang, Korea.
Seok Cheol
SC
Lee
Biomolecular Function Research Branch, National Cancer Center, Goyang, Korea.
Su Jin
SJ
Oh
Biomolecular Function Research Branch, National Cancer Center, Goyang, Korea.
Seok Hoon
SH
Jang
Molecular Imaging and Therapy Branch, National Cancer Center, Goyang, Korea.
In Hoo
IH
Kim
Department of Veterinary Pathology, College of Veterinary Medicine, Seoul National University, Seoul, Korea.
Dae Yong
DY
Kim
Biomolecular Function Research Branch, National Cancer Center, Goyang, Korea.
Hark Kyun
HK
Kim
Hollow fiber assay; Liver neoplasms; Stomach neoplasms; Xenograft model antitumor assay