In vitro augmentation of antitumor effect in combination with CPT-11 and CDDP for human colorectal cancer.
OBJECTIVE
Irinotecan hydrochloride (CPT-11) is one of the camptothecin analogues that has shown a broad spectrum of strong antitumor effectiveness against various cancers, including colorectal cancer. In order to promote the clinical response of chemotherapy for colorectal cancer using CPT-11, one of the most effective strategies is to use it in combination with other anticancer agents. In the present study, anticancer effects after combining CPT-11 and other antitumor agents were determined by a 3-(4,5-di-methylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay of colorectal cancer cells, especially freshly isolated cancer cells.


METHODS
Freshly isolated cancer cells from 20 patients with colorectal cancer and the established colon cancer cell lines were used in this study. The augmentation of the antitumor effectiveness of 7-ethyl-10-hydroxy-CPT (SN-38) was analyzed in combination with other anticancer agents. Furthermore, the antitumor effectiveness using lower concentrations of anticancer agents was measured to understand the mechanism of the augmentation.


RESULTS
The percent inhibition of SN-38 in combination with cisplatin (CDDP) and mitomycin revealed a high anticancer effect compared with each anticancer agent alone for freshly isolated rectal cancer. CDDP also had a synergistic effect in combination with SN-38 according to the fractional product concept. At lower than plasma peak concentrations of SN-38, the anticancer effects were augmented in combination with lower concentrations of CDDP for freshly isolated colorectal cancer. This augmentation showed a strong synergistic effect.


CONCLUSIONS
These results may be supportive to ongoing clinical studies of chemotherapy by using CPT-11 and CDDP for advanced colorectal cancer.
Tsunoda
T
T
Second Department of Surgery, Wakayama Medical School, Wakayama, Japan. tsuntsun@wakayama-med.ac.jp
Tanimura
H
H
Hotta
T
T
Tani
M
M
Iwahashi
M
M
Ishimoto
K
K
Tanaka
H
H
Matsuda
K
K
Yamaue
H
H
D000230:Adenocarcinoma / Q000188:drug therapy*; D000903:Antibiotics, Antineoplastic / Q000008:administration & dosage; D000970:Antineoplastic Agents / Q000008:administration & dosage*; D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage* / Q000097:blood; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D002166:Camptothecin / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000097:blood; D002945:Cisplatin / Q000008:administration & dosage*; D003110:Colonic Neoplasms / Q000188:drug therapy*; D004396:Coloring Agents; D004357:Drug Synergism; D005260:Female; D006801:Humans; D000077146:Irinotecan; D008297:Male; D008875:Middle Aged; D016685:Mitomycin / Q000008:administration & dosage; D012004:Rectal Neoplasms / Q000188:drug therapy*; D013778:Tetrazolium Salts; D013844:Thiazoles; D014407:Tumor Cells, Cultured
D000903:Antibiotics, Antineoplastic; D000970:Antineoplastic Agents; D000972:Antineoplastic Agents, Phytogenic; D004396:Coloring Agents; D013778:Tetrazolium Salts; D013844:Thiazoles; D016685:Mitomycin; D000077146:Irinotecan; C022616:thiazolyl blue; D002945:Cisplatin; D002166:Camptothecin