Abstract
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% CO 2 atmosphere at 37°C. 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.
| Original language | English |
|---|---|
| Pages (from-to) | 3893-3897 |
| Number of pages | 5 |
| Journal | Anticancer Research |
| Volume | 24 |
| Issue number | 6 |
| Publication status | Published - Nov 2004 |
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Keywords
- Cisplatin
- Irinotecan
- Lung cancer
- Topoisomerase I
ASJC Scopus subject areas
- Cancer Research
- Oncology
Cite this
Cisplatin down-regulates topoisomerase I activity in lung cancer cell lines. / Aoe, Keisuke; Kiura, Katsuyuki; Ueoka, Hiroshi; Tabata, Masahiro; Chikamori, Masakazu; Kohara, Hiroyuki; Harada, Mine; Tanimoto, Mitsune.
In: Anticancer Research, Vol. 24, No. 6, 11.2004, p. 3893-3897.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Cisplatin down-regulates topoisomerase I activity in lung cancer cell lines
AU - Aoe, Keisuke
AU - Kiura, Katsuyuki
AU - Ueoka, Hiroshi
AU - Tabata, Masahiro
AU - Chikamori, Masakazu
AU - Kohara, Hiroyuki
AU - Harada, Mine
AU - Tanimoto, Mitsune
PY - 2004/11
Y1 - 2004/11
N2 - 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% CO 2 atmosphere at 37°C. 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.
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% CO 2 atmosphere at 37°C. 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.
KW - Cisplatin
KW - Irinotecan
KW - Lung cancer
KW - Topoisomerase I
UR - http://www.scopus.com/inward/record.url?scp=14944348037&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=14944348037&partnerID=8YFLogxK
M3 - Article
C2 - 15736428
AN - SCOPUS:14944348037
VL - 24
SP - 3893
EP - 3897
JO - Anticancer Research
JF - Anticancer Research
SN - 0250-7005
IS - 6
ER -