TY - JOUR
T1 - Isolation and characterization of gemcitabine-resistant human non-small cell lung cancer A549 cells
AU - Ikeda, Ryuji
AU - Vermeulen, Lee C.
AU - Lau, Elim
AU - Jiang, Zhisheng
AU - Sachidanandam, Kamakshi
AU - Yamada, Katsushi
AU - Kolesar, Jill M.
PY - 2011/2
Y1 - 2011/2
N2 - Gemcitabine is an effective chemotherapy against non-small cell lung cancer (NSCLC). However, resistance to gemcitabine reduces its efficacy. We have isolated gemcitabineresistant human non-small cell lung cancer A549 cells, termed A549/GR cells. A549/GR cells were resistant to gemcitabine as well as paclitaxel and docetaxel but not carboplatin and irinotecan. The expression level of multidrug resistance protein 7 (MRP7) in A549/GR cells was higher than that in A549 cells, and the inhibitor of MRP7 by cepharanthine increased the sensitivity to gemcitabine in A549/GR cells. These findings indicate that cepharanthine reversed gemcitabine resistance. To determine predictive molecular markers of gemcitabine resistance for more effective treatment of these tumors, we performed PCR array. We identified that CDKN1A/p21, CYP3A5, microsomal epoxide hyrolase 1 (EPHX1) and ABCC6 (MRP6) were up-regulated >5-fold in A549/GR cells. Gemcitabine also induced the expression of p21 and CYP3A5 in A549 cells. A better understanding of the characterization and mechanism of the resistance to gemcitabine in A549/GR cells may help identify agents that reverse clinical gemcitabine resistance in NSCLC.
AB - Gemcitabine is an effective chemotherapy against non-small cell lung cancer (NSCLC). However, resistance to gemcitabine reduces its efficacy. We have isolated gemcitabineresistant human non-small cell lung cancer A549 cells, termed A549/GR cells. A549/GR cells were resistant to gemcitabine as well as paclitaxel and docetaxel but not carboplatin and irinotecan. The expression level of multidrug resistance protein 7 (MRP7) in A549/GR cells was higher than that in A549 cells, and the inhibitor of MRP7 by cepharanthine increased the sensitivity to gemcitabine in A549/GR cells. These findings indicate that cepharanthine reversed gemcitabine resistance. To determine predictive molecular markers of gemcitabine resistance for more effective treatment of these tumors, we performed PCR array. We identified that CDKN1A/p21, CYP3A5, microsomal epoxide hyrolase 1 (EPHX1) and ABCC6 (MRP6) were up-regulated >5-fold in A549/GR cells. Gemcitabine also induced the expression of p21 and CYP3A5 in A549 cells. A better understanding of the characterization and mechanism of the resistance to gemcitabine in A549/GR cells may help identify agents that reverse clinical gemcitabine resistance in NSCLC.
KW - A549 cells
KW - Gemcitabine
KW - Non-small cell lung cancer
UR - http://www.scopus.com/inward/record.url?scp=78651237278&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=78651237278&partnerID=8YFLogxK
U2 - 10.3892/ijo.2010.866
DO - 10.3892/ijo.2010.866
M3 - Article
C2 - 21152861
AN - SCOPUS:78651237278
SN - 1019-6439
VL - 38
SP - 513
EP - 519
JO - International Journal of Oncology
JF - International Journal of Oncology
IS - 2
ER -