[Correlation of sorcin overexpression to multidrug resistance of human gastric cancer cell line SGC7901].
OBJECTIVE
Vincristine (VCR)-resistant gastric cancer cell line SGC7901/VCR is a typical multidrug resistant (MDR) cell line with high expression of P-glycoprotein (P-gp). However, verapamil (VRP), the inhibitor of P-gp, can not totally reverse the drug resistance, indicating that additional mechanisms must contribute to the MDR phenotype. Our previous study showed that sorcin, a calcium-binding protein, is significantly up-regulated in SGC7901/VCR cells. This study was to explore the role of sorcin in the development of MDR in human gastric cancer cell line SGC7901.


METHODS
The full length sorcin cDNA was isolated by reverse transcription-polymerase chain reaction (RT-PCR). The FLAG-sorsin-pcDNA3.1 plasmid was constructed and transfected into SGC7901 cells. The mRNA and protein levels of sorcin in stable clones were detected by RT-PCR and Western blot. The sensitivity of SGC7901 cells to chemotherapeutic drugs was detected using MTT assay. Then sorcin-transfected SGC7901 cells (SGC-F-Sor) were transfected with sorcin antisense oligonucleotides (ASO). The VCR-sensitivity of SGC7901 cells was determined by MTT assay.


RESULTS
The full-length sorcin cDNA (616 bp) was amplified by RT-PCR. The FLAG-sorsin-pcDNA3.1 plasmid was constructed successfully. The mRNA and protein levels of sorcin were up-regulated in SGC-F-Sor cells. Overexpression of sorcin produced 8.87 folds of VCR-resistance, 6.13 folds of adriamycin (ADM)-resistance, 6.67 folds of taxol-resistance, and 2.80 folds of 5-fluorouracil (5-FU)-resistance. However, when SGC-F-Sor cells were transfected with sorcin ASO, down-regulation of sorcin expression and increased sensitivity to VCR were observed.


CONCLUSIONS
Overexpression of sorcin could induce low level of MDR in SGC7901 cells, indicating that sorcin is associated with MDR of SGC7901 cells. Sorcin maybe be a target of MDR reversal in gastric cancer cells.
He
Qing-Chun
QC
Department of Digestive Diseases, Xiangya Hospital, Central South University, Changsha, Hunan, 410008, PR China.
Zhang
Gui-Ying
GY
Cao
Wei-Jun
WJ
D002135:Calcium-Binding Proteins / Q000032:analysis / Q000235:genetics / Q000502:physiology*; D045744:Cell Line, Tumor; D019008:Drug Resistance, Neoplasm; D006801:Humans; D012333:RNA, Messenger / Q000032:analysis; D013274:Stomach Neoplasms / Q000188:drug therapy* / Q000473:pathology
D002135:Calcium-Binding Proteins; D012333:RNA, Messenger; C503113:SRI protein, human