Silencing MRP4 by small interfering RNA reverses acquired DDP resistance of gastric cancer cell.
A cisplatin (DDP) resistant cell line (SGC7901/DDP) from a Chinese gastric cancer cell line (SGC7901) was established by step-increasing DDP treatment, and the resultant cell line showed an over 21.9-fold increased resistance to DDP. To identify the mechanism of DDP resistance, the differential gene expression panel was examined by Affymetrix microarray. Among the identified differential genes, 681 genes expression were increased and 1139 genes were decreased. To confirm these gene changes furtherly, one of the upregulated gene, MRP4 was identified with increased mRNA and protein level of SGC7901/DDP by RT-PCR and Western-blot analysis compared with its parental cell line. By using the small interfering RNA (RNAi) to decrease the MRP4 expression, the DDP resistance phenotype of SGC7901/DDP was reversed. These data suggest that MRP4 is a DDP resistance candidate gene of SGC7901 gastric cancer cell line.
Zhang
Yan-Hong
YH
Department of Oncology, Xuhui Central Hospital, Shanghai, China. yanhonzhang@126.com
Wu
Qing
Q
Xiao
Xiu-Ying
XY
Li
Da-Wei
DW
Wang
Xing-Peng
XP
D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D001483:Base Sequence; D045744:Cell Line, Tumor; D002945:Cisplatin / Q000494:pharmacology*; D019008:Drug Resistance, Neoplasm; D020869:Gene Expression Profiling; D006801:Humans; D008969:Molecular Sequence Data; D027425:ATP-Binding Cassette, Sub-Family C Proteins / Q000037:antagonists & inhibitors* / Q000235:genetics; D034741:RNA, Small Interfering / Q000235:genetics*; D013274:Stomach Neoplasms / Q000188:drug therapy* / Q000473:pathology
D000970:Antineoplastic Agents; D002945:Cisplatin; D027425:ATP-Binding Cassette, Sub-Family C Proteins; D034741:RNA, Small Interfering; C073492:ABCC4 protein, human