Prediction of 5-fluorouracil and cisplatin synergism for advanced gastrointestinal cancers using a collagen gel droplet embedded culture.
OBJECTIVE
The combination effects of 5-fluorouracil (5-FU) and cisplatin (CDDP) are herein reported using a drug sensitivity assay, with a special focus on the induction of apoptosis.


METHODS
The combination effects of 5-FU and CDDP were examined using in vitro chemosensitivity testing by means of the collagen gel droplet embedded culture drug sensitivity test (CD-DST) in MKN45 and GSS cell lines, and primary gastrointestinal cancer cells ob-tained from 40 patients. Apoptosis was assayed using the terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate biotin neck end labeling (TUNEL) method.


RESULTS
The combination of 5-FU with CDDP increased the efficacy of 5-FU 1.16-1.35-fold with the GSS cell line and 1.10-2.01-fold with primary gastric and colorectal cancers when the exposure time was 7 days. In primary tumor cells a synergistic action was noted in 15 of 40 (38%) gastric and colorectal cancers. Both 5-FU and CDDP were found to induce apoptosis in GSS and MKN45 cells, and the number of apoptotic cells increased synergistically after the combined treatment in the GSS cases and showed a correlation with the results of CD-DST.


CONCLUSIONS
Our findings suggested that the efficacy of the combined treatment with 5-FU and CDDP can be predicted by the in vitro chemosensitivity test and that a synergistic effect might be associated with the induction of apoptosis.
Mori
Shigeru
S
Department of Tumor and General Surgery, Gifu University School of Medicine, 40 Tukasa-machi, 500-8705, Gifu, Japan.
Kunieda
Katsuyuki
K
Sugiyama
Yasuyuki
Y
Saji
Shigetoyo
S
D000368:Aged; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D017209:Apoptosis; D002945:Cisplatin / Q000008:administration & dosage / Q000627:therapeutic use*; D003094:Collagen; D004354:Drug Screening Assays, Antitumor; D004357:Drug Synergism; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage / Q000627:therapeutic use*; D005770:Gastrointestinal Neoplasms / Q000188:drug therapy*; D005782:Gels; D006801:Humans; D020287:In Situ Nick-End Labeling; D008297:Male; D008875:Middle Aged; D014407:Tumor Cells, Cultured / Q000187:drug effects
D000970:Antineoplastic Agents; D005782:Gels; D003094:Collagen; D002945:Cisplatin; D005472:Fluorouracil