PT  - JOURNAL ARTICLE
AU  - KEISUKE AOE
AU  - KATSUYUKI KIURA
AU  - HIROSHI UEOKA
AU  - MASAHIRO TABATA
AU  - MASAKAZU CHIKAMORI
AU  - HIROYUKI KOHARA
AU  - MINE HARADA
AU  - MITSUNE TANIMOTO
TI  - Cisplatin Down-regulates Topoisomerase I Activity in Lung Cancer Cell Lines
DP  - 2004 Nov 01
TA  - Anticancer Research
PG  - 3893--3898
VI  - 24
IP  - 6
4099  - http://ar.iiarjournals.org/content/24/6/3893.short
4100  - http://ar.iiarjournals.org/content/24/6/3893.full
SO  - Anticancer Res2004 Nov 01; 24
AB  - Many clinical studies have reported that irinotecan has reproducible antitumor activity against lung cancer. Both cisplatin and SN-38 are key drugs in the treatment of lung cancer, and their combination is one of the most promising regimens available. Using lung cancer cell lines, ABC-1 and SBC-3, we examined the cytotoxic effect of the schedule, as well as the effect of cisplatin on topoisomerase I activity. Cytotoxicity was determined by MTT assay. ABC-1 or SBC-3 cells were incubated with or without various concentrations of both drugs in 96-well microplates for 72 or 96 hours in a humidified 5% CO2 atmosphere at 37ÆC. Synergism was evaluated by median-effect plot analysis and a combination index isobologram method by Chou and Talalay. After ABC-1 or SBC-3 cells had been exposed to 10 μM cisplatin for one hour, topoisomerase I activities were determined by supercoiled-DNA relaxation assay. Synergism was observed in ABC-1 and SBC-3 cells when cisplatin was given first, followed by SN-38 (7-ethyl-10-hydroxycamptothecin) and cisplatin. Topoisomerase I activity decreased at 1-2 hours after exposure to cisplatin and recovered gradually after 4-5 hours of cisplatin exposure in both ABC-1 and SBC-3 cells. Accordingly, pretreatment with cisplatin will have an impact on the sensitivity to SN-38. Copyright© 2004 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved