Abstract
The interaction between CPT-11 and oxaliplatin, a new platinum derivative that has a great antitumor activity against colon cancer, has not been determined in gastric cancer cells. In this study, we investigated in vitro cytotoxic activity of oxaliplatin alone or in combination with SN-38, an active metabolite of CPT-11, using different exposure schedules in three human gastric cancer cell lines (AZ-521, MKN-45, and NUGC-4). Cytotoxicity was determined by WST-1 assay. Different treatment schedules of the two drugs were compared and evaluated for synergism, additivity, or antagonism with a quantitative method based on the median-effect principle of Chou and Talalay. Cell cycle perturbation was evaluated by flow cytometry. In 24-h exposure, simultaneous administration of oxaliplatin and SN-38 showed a synergistic effect in AZ-521 and NUGC-4 cells, and an additive effect in MKN-45 cells. Greater than additive effects were observed in all of the cell lines when cells were treated with oxaliplatin followed by SN-38, whereas such effects were observed only in NUGC-4 cells in the reverse sequence. Flow cytometric analyses at IC50 indicated that apoptosis was most prominent in simultaneous exposures with accumulation of cells in both G0/G1 and S phases. These results suggest that SN-38 may kill the cells recovering from the G1 block produced by oxaliplatin as they progress into the S phase. Simultaneous administration appears most active in gastric cancer cell lines. These results may provide important information for a clinical trial of oxaliplatin and CPT-11 combination for patients with gastric cancer.
| Original language | English |
|---|---|
| Pages (from-to) | 683-688 |
| Number of pages | 6 |
| Journal | Oncology Reports |
| Volume | 14 |
| Issue number | 3 |
| Publication status | Published - Sep 1 2005 |
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All Science Journal Classification (ASJC) codes
- Oncology
- Cancer Research
Cite this
Synergistic interaction between oxaliplatin and SN-38 in human gastric cancer cell lines in vitro. / Tanaka, Risa; ariyama, hiroshi; Qin, Baoli; Shibata, Yoshihiro; Takii, Yasushi; Kusaba, Hitoshi; Baba, Eishi; Mitsugi, Kenji; Harada, Mine; Nakano, Shuji.
In: Oncology Reports, Vol. 14, No. 3, 01.09.2005, p. 683-688.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Synergistic interaction between oxaliplatin and SN-38 in human gastric cancer cell lines in vitro
AU - Tanaka, Risa
AU - ariyama, hiroshi
AU - Qin, Baoli
AU - Shibata, Yoshihiro
AU - Takii, Yasushi
AU - Kusaba, Hitoshi
AU - Baba, Eishi
AU - Mitsugi, Kenji
AU - Harada, Mine
AU - Nakano, Shuji
PY - 2005/9/1
Y1 - 2005/9/1
N2 - The interaction between CPT-11 and oxaliplatin, a new platinum derivative that has a great antitumor activity against colon cancer, has not been determined in gastric cancer cells. In this study, we investigated in vitro cytotoxic activity of oxaliplatin alone or in combination with SN-38, an active metabolite of CPT-11, using different exposure schedules in three human gastric cancer cell lines (AZ-521, MKN-45, and NUGC-4). Cytotoxicity was determined by WST-1 assay. Different treatment schedules of the two drugs were compared and evaluated for synergism, additivity, or antagonism with a quantitative method based on the median-effect principle of Chou and Talalay. Cell cycle perturbation was evaluated by flow cytometry. In 24-h exposure, simultaneous administration of oxaliplatin and SN-38 showed a synergistic effect in AZ-521 and NUGC-4 cells, and an additive effect in MKN-45 cells. Greater than additive effects were observed in all of the cell lines when cells were treated with oxaliplatin followed by SN-38, whereas such effects were observed only in NUGC-4 cells in the reverse sequence. Flow cytometric analyses at IC50 indicated that apoptosis was most prominent in simultaneous exposures with accumulation of cells in both G0/G1 and S phases. These results suggest that SN-38 may kill the cells recovering from the G1 block produced by oxaliplatin as they progress into the S phase. Simultaneous administration appears most active in gastric cancer cell lines. These results may provide important information for a clinical trial of oxaliplatin and CPT-11 combination for patients with gastric cancer.
AB - The interaction between CPT-11 and oxaliplatin, a new platinum derivative that has a great antitumor activity against colon cancer, has not been determined in gastric cancer cells. In this study, we investigated in vitro cytotoxic activity of oxaliplatin alone or in combination with SN-38, an active metabolite of CPT-11, using different exposure schedules in three human gastric cancer cell lines (AZ-521, MKN-45, and NUGC-4). Cytotoxicity was determined by WST-1 assay. Different treatment schedules of the two drugs were compared and evaluated for synergism, additivity, or antagonism with a quantitative method based on the median-effect principle of Chou and Talalay. Cell cycle perturbation was evaluated by flow cytometry. In 24-h exposure, simultaneous administration of oxaliplatin and SN-38 showed a synergistic effect in AZ-521 and NUGC-4 cells, and an additive effect in MKN-45 cells. Greater than additive effects were observed in all of the cell lines when cells were treated with oxaliplatin followed by SN-38, whereas such effects were observed only in NUGC-4 cells in the reverse sequence. Flow cytometric analyses at IC50 indicated that apoptosis was most prominent in simultaneous exposures with accumulation of cells in both G0/G1 and S phases. These results suggest that SN-38 may kill the cells recovering from the G1 block produced by oxaliplatin as they progress into the S phase. Simultaneous administration appears most active in gastric cancer cell lines. These results may provide important information for a clinical trial of oxaliplatin and CPT-11 combination for patients with gastric cancer.
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UR - http://www.scopus.com/inward/citedby.url?scp=24644485386&partnerID=8YFLogxK
M3 - Article
C2 - 16077975
AN - SCOPUS:24644485386
VL - 14
SP - 683
EP - 688
JO - Oncology Reports
JF - Oncology Reports
SN - 1021-335X
IS - 3
ER -