RT Journal Article
SR Electronic
T1 Oxaliplatin in Treatment of the Cisplatin-resistant MKN45 Cell Line of Gastric Cancer
JF Anticancer Research
JO Anticancer Res
FD International Institute of Anticancer Research
SP 2087
OP 2092
VO 28
IS 4B
A1 KATSUYUKI TOZAWA
A1 TADAYUKI OSHIMA
A1 TAKEHIKO KOBAYASHI
A1 NORIYASU YAMAMOTO
A1 CHIZUKO HAYASHI
A1 TAKAYUKI MATSUMOTO
A1 HIROTO MIWA
YR 2008
UL http://ar.iiarjournals.org/content/28/4B/2087.abstract
AB 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)-π 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-π 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-π 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. Copyright© 2008 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved