Abstract:
BACKGROUND AND AIM:The clinical efficiency of cisplatin (CDDP) against gastric cancer is often limited by the development of resistance. A third-generation platinum-containing agent, oxaliplatin (L-OHP), has been introduced for treating gastric cancer. Here, we studied oxaliplatin in vitro to reveal the mechanism of acquiring drug resistance and whether a cisplatin-resistant gastric cancer cell line has susceptibility to oxaliplatin. MATERIALS AND METHODS:A cisplatin-resistant gastric cancer cell line (MKN45/CDDP/ R1) was established by continuous exposure of MKN45 cells to cisplatin. The amount of excision repair cross-complementation group 1 (ERCC1) and glutathione-S-transferase (GST)-pi mRNA was measured by real-time polymerase chain reaction (PCR). To examine the chemosensitivity to CDDP and L-OHP in MKN45 and MKN45/CDDP/R1 cells, a collagen gel droplet-embedded culture drug sensitivity test (CD-DST) was performed. The intracellular concentration of CDDP and L-OHP were also measured to see if the drugs would be taken up by these cell lines. RESULTS:The MKN45/CDDP/R1 cell line was resistant to CDDP. The ERCC1 and GST-pi mRNA was significantly increased in MKN45/CDDP/R1 cells, indicating that the cells acquired resistance to CDDP. Intracellular CDDP was not detected in MKN45/CDDP/R1 cells up to 48 h after incubation, indicating that uptake and efflux processes of CDDP were altered in these cells. MKN45/CDDP/R1 cells were still susceptible to L-OHP. The intracellular concentration of CDDP but not L-OHP was significantly reduced in MKN45/CDDP/R1 cells. CONCLUSION:We established a CDDP-resistant cell line using MKN45 cells, in which ERCC1 and GST-pi were increased. This cell line showed susceptibility to the new generation platinum agent L-OHP, suggesting this anticancer agent could be used in second-line treatment of patients with CDDP-resistant gastric neoplasms.
journal_name
Anticancer Resjournal_title
Anticancer researchauthors
Tozawa K,Oshima T,Kobayashi T,Yamamoto N,Hayashi C,Matsumoto T,Miwa Hsubject
Has Abstractpub_date
2008-07-01 00:00:00pages
2087-92issue
4Beissn
0250-7005issn
1791-7530journal_volume
28pub_type
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journal_title:Anticancer research
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journal_title:Anticancer research
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journal_title:Anticancer research
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journal_title:Anticancer research
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journal_title:Anticancer research
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journal_title:Anticancer research
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journal_title:Anticancer research
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doi:
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journal_title:Anticancer research
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doi:
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更新日期:2003-11-01 00:00:00
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journal_title:Anticancer research
pub_type: 杂志文章
doi:
更新日期:1991-03-01 00:00:00
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journal_title:Anticancer research
pub_type: 杂志文章
doi:
更新日期:2004-09-01 00:00:00
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journal_title:Anticancer research
pub_type: 杂志文章
doi:
更新日期:1996-07-01 00:00:00
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journal_title:Anticancer research
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doi:
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journal_title:Anticancer research
pub_type: 杂志文章
doi:
更新日期:2014-08-01 00:00:00
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journal_title:Anticancer research
pub_type: 杂志文章
doi:
更新日期:1989-03-01 00:00:00
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journal_title:Anticancer research
pub_type: 杂志文章
doi:
更新日期:1999-05-01 00:00:00
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journal_title:Anticancer research
pub_type: 杂志文章
doi:
更新日期:1994-09-01 00:00:00
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更新日期:2019-05-01 00:00:00
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pub_type: 杂志文章
doi:
更新日期:2002-05-01 00:00:00