Reversal of multidrug resistance of gastric cancer cells by downregulation of TSG101 with TSG101siRNA.
We have previously identified tumor susceptibility gene101 (TSG101), overexpressed in vincristine-resistant human gastric adenocarcinoma cell line SGC7901/VCR using a modified subtractive hybridization method and Western blot. In the present study, we constructed two siRNA eukaryotic expression vectors of TSG101 and transfected them into SGC7901/VCR cells to examine whether the down-regulation of TSG101 increased cell sensitivity towards chemotherapeutic drugs. After transfection, the expression of TSG101 was dramatically decreased in TSG101 siRNA transfectants compared with that in parental cells and empty vector control cells. The down-regulation of TSG101 could significantly enhance the sensitivity of SGC7901/VCR cells to vincristine and adriamycin. The capacity of cells to efflux adriamycin markedly decreased in TSG101 siRNA transfectants. These observations suggested that the siRNA constructs of TSG101 we made could effectively down-regulate the expression of TSG101 and reverse the resistant phenotype of gastric cancer cells. The preliminary study suggested that TSG101 might play an important role in multidrug resistance of gastric carcinoma.
Shen
Huiqin
H
Institute of Digestive Diseases, Xijing Hospital, Fourth Military Medical University, Xi'an 710032, Shaanxi Province, People's Republic of China.
Pan
Yanglin
Y
Han
Zheyi
Z
Hong
Liu
L
Liu
Na
N
Han
Shuang
S
Yao
Liping
L
Xie
Huahong
H
Zhaxi
Cuomu
C
Shi
Yongquan
Y
Fan
Daiming
D
D000970:Antineoplastic Agents / Q000494:pharmacology*; D004268:DNA-Binding Proteins / Q000235:genetics* / Q000378:metabolism*; D015536:Down-Regulation; D004317:Doxorubicin / Q000494:pharmacology; D018432:Drug Resistance, Multiple; D019008:Drug Resistance, Neoplasm; D056827:Endosomal Sorting Complexes Required for Transport; D006801:Humans; D016350:Leucine Zippers; D034741:RNA, Small Interfering / Q000378:metabolism*; D013274:Stomach Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics* / Q000378:metabolism*; D014162:Transfection; D014407:Tumor Cells, Cultured; D014750:Vincristine / Q000494:pharmacology; D000099177:Tsg101 Protein
D000970:Antineoplastic Agents; D004268:DNA-Binding Proteins; D004317:Doxorubicin; D056827:Endosomal Sorting Complexes Required for Transport; D034741:RNA, Small Interfering; D014157:Transcription Factors; D014750:Vincristine; D000099177:Tsg101 Protein