ABCC10/MRP7 is associated with vinorelbine resistance in non-small cell lung cancer.
The non-small cell lung cancer (NSCLC) cells SK-LC6 and NCI-H23 were continuously exposed to vinorelbine (VNB), and the VNB-resistant clones, SK-LC6/VNB and H23/VNB were selected. Since SK-LS6/VNB and H23/VNB cells showed cross-resistance to certain anticancer drugs, such as paclitaxel and docetaxel, we examined the gene expression levels of drug efflux transporters of the ATP-binding cassette (ABC) family. We found that the gene expression of ABCB1/MDR1 and ABCC10/MRP7 in SK-LC6/VNB and H23/VNB cells was increased compared with that in SK-LS6 and NCI-H23 cells, whereas the expression of ABCC1/MRP1, ABCC2/MRP2, ABCC3/MRP3 and ABCG2/BCRP did not change among these cells. Treatment with ABCB1/MDR1 inhibitor verapamil and ABCC10/MRP7 inhibitor sulfin-pyrazone altered the sensitivity of SK-LC6/VNB cells to vinorelbine. To confirm the ABCC10/MRP7 activity, we transfected small interfering RNA against ABCC10/MRP7 to ABCC10/MRP7-expressing RERF-LC-AI cells resulting in the decrease of ABCC10/MRP7 expression concomitant with the alteration of VNB cytotoxicity. Moreover, we detected the expression of ABCC10/MRP7 in 12 of 17 NSCLC cells, whereas ABCB1/MDR1 was detected in only 3 of 17 NSCLC cells. These results indicate that ABCC10/MRP7 may confer VNB resistance in NSCLC.
Bessho
Yuji
Y
Department of Medical Oncology and Immunology, Nagoya City University Graduate School of Medical Sciences, Nagoya 467-8601, Japan.
Oguri
Tetsuya
T
Ozasa
Hiroaki
H
Uemura
Takehiro
T
Sakamoto
Hideo
H
Miyazaki
Mikinori
M
Maeno
Ken
K
Sato
Shigeki
S
Ueda
Ryuzo
R
D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology*; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy / Q000235:genetics*; D045744:Cell Line, Tumor; D019008:Drug Resistance, Neoplasm / Q000235:genetics*; D015870:Gene Expression; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy / Q000235:genetics*; D000089762:Multidrug Resistance-Associated Protein 2; D027425:ATP-Binding Cassette, Sub-Family C Proteins / Q000096:biosynthesis / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014747:Vinblastine / Q000031:analogs & derivatives* / Q000494:pharmacology; D000077235:Vinorelbine
D000972:Antineoplastic Agents, Phytogenic; D000089762:Multidrug Resistance-Associated Protein 2; D027425:ATP-Binding Cassette, Sub-Family C Proteins; D014747:Vinblastine; D000077235:Vinorelbine; C421142:ABCC10 protein, human; C000715087:ABCC2 protein, human