title: Effects of 5-fluorouracil, adriamycin and irinotecan on HSC-39, a human scirrhous gastric cancer cell line.
abstract: Therapies for patients with scirrhous gastric cancer remain ineffective. Current treatments for gastric cancer based on systemic therapy, such as the combination of S-1 with cisplatin or docetaxel, show good clinical response rates. S-1 plus cisplatin is the standard treatment for HER2-negative advanced scirrhous gastric cancer in Japan. In spite of recent advances in the treatment of gastric cancer, a standard chemotherapy regimen is yet to be established for scirrhous gastric cancer. To develop new therapeutic approaches based on characteristic biological features of cancer cells, we examined the mechanisms underlying the cytotoxicity of anticancer drugs and reactive oxygen species (ROS) toward a human scirrhous cancer cell line, HSC-39, in vitro. Anticancer drugs such as 5-fluorouracil (5-FU), adriamycin (ADR) and irinotecan (CPT-11), as well as ROS, were previously shown to have important cytotoxic effects on these tumor cells. We demonstrated that 5-FU effectively induced apoptosis in HSC-39 cells in a dose‑dependent manner, while ADR and CPT-11 induced necrosis and/or aponecrosis. 5-FU effectively inhibited WST-1 decrease in the MTT viability assay, even at low doses where little LDH release was observed, while ADR and CPT-11 only inhibited WST-1 decrease at high doses where LDH release was induced. Moreover, HSC-39 cells showed high sensitivity to H2O2 and NOC-18, but less sensitivity to other ROS, suggesting a link between cell damage and membrane permeability changes induced by H2O2 and NOC-18 or related oxygen radical species such as OH· or ·O2. These results suggest that combination treatment of chemotherapeutics with a fluoropyrimidine such as 5-FU is effective chemotherapy for scirrhous gastric cancer.
authors.affiliation: Laboratory of Biodefense and Regulation, Osaka University of Pharmaceutical Sciences, Takatsuki, Osaka, Japan.
authors.forename: Rie
authors.initials: R
authors.lastname: Tamaki
authors.affiliation: Laboratory of Biodefense and Regulation, Osaka University of Pharmaceutical Sciences, Takatsuki, Osaka, Japan.
authors.forename: Aya
authors.initials: A
authors.lastname: Kanai-Mori
authors.affiliation: Laboratory of Biodefense and Regulation, Osaka University of Pharmaceutical Sciences, Takatsuki, Osaka, Japan.
authors.forename: Yuta
authors.initials: Y
authors.lastname: Morishige
authors.affiliation: Laboratory of Biodefense and Regulation, Osaka University of Pharmaceutical Sciences, Takatsuki, Osaka, Japan.
authors.forename: Atsushi
authors.initials: A
authors.lastname: Koike
authors.affiliation: Laboratory of Biodefense and Regulation, Osaka University of Pharmaceutical Sciences, Takatsuki, Osaka, Japan.
authors.forename: Kazuyoshi
authors.initials: K
authors.lastname: Yanagihara
authors.affiliation: Laboratory of Biodefense and Regulation, Osaka University of Pharmaceutical Sciences, Takatsuki, Osaka, Japan.
authors.forename: Fumio
authors.initials: F
authors.lastname: Amano
mesh_terms: D002293:Adenocarcinoma, Scirrhous / Q000188:drug therapy / Q000378:metabolism*; D017209:Apoptosis; D002166:Camptothecin / Q000031:analogs & derivatives* / Q000494:pharmacology; D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004317:Doxorubicin / Q000494:pharmacology*; D004359:Drug Therapy, Combination; D005472:Fluorouracil / Q000494:pharmacology*; D006801:Humans; D000077146:Irinotecan; D008297:Male; D008875:Middle Aged; D009336:Necrosis; D017382:Reactive Oxygen Species / Q000378:metabolism*; D013274:Stomach Neoplasms / Q000188:drug therapy / Q000378:metabolism*
chemical_list: D017382:Reactive Oxygen Species; D000077146:Irinotecan; D004317:Doxorubicin; D005472:Fluorouracil; D002166:Camptothecin