Overexpression of sorcin results in multidrug resistance in gastric cancer cells with up-regulation of P-gp.
Sorcin, a calcium-binding protein was found up-regulated in the vincristine-induced multi-drug resistance (MDR) gastric cancer cell line SGC7901/VCR, over its parental SGC7901 cells in our previous proteomic studies. The present study explored the role and mechanism of sorcin in the development of MDR in gastric cancer. We constructed the recombinant plasmids FLAG-sorsin-pcDNA3.1 containing the full open reading frame of sorcin and a FLAG affinity tag. Overexpression of sorcin by gene transfection was able to confer drug resistance to vincristine, adriamycin, taxol and 5-fluorouracil in SGC7901 cells. Down-regulation of sorcin expression by sorcin antisense oligonucleutides, (ASO) increased sensitivity to vincristine. The intracellular concentration of vincristine in SGC7901 cells decreased in sorcin transfected cells and increased in sorcin ASO-transfected cells, indicating that sorcin had a direct or indirect function on pumping the drug out of cells. Overexpression of sorcin up-regulated the expression of P-gp and P-gp inhibitor verapamil partially reversed the sorcin-mediated MDR in SGC7901 cell, suggesting that regulation of P-gp might be one of the mechanisms of sorcin-mediated MDR. The further study of the interaction protein of sorcin may be helpful for understanding the mechanisms of MDR in gastric cancer and developing possible strategies to treat gastric cancer.
Department of Emergency, Central South University, Changsha, Hunan Province, P.R. China.
Qingchun
Q
He
Guiying
G
Zhang
Defu
D
Hou
Aiming
A
Leng
Meihua
M
Xu
Jie
J
Peng
Ting
T
Liu
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000096:biosynthesis* / Q000235:genetics; D015153:Blotting, Western; D002135:Calcium-Binding Proteins / Q000096:biosynthesis* / Q000235:genetics; D045744:Cell Line, Tumor; D002851:Chromatography, High Pressure Liquid; D018432:Drug Resistance, Multiple / Q000235:genetics*; D019008:Drug Resistance, Neoplasm / Q000235:genetics*; D006801:Humans; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013274:Stomach Neoplasms / Q000235:genetics* / Q000378:metabolism; D014162:Transfection; D015854:Up-Regulation
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D002135:Calcium-Binding Proteins; C503113:SRI protein, human