Establishment Of An Oxaliplatin-resistant Human Gastric Carcinoma SGC-7901/L-OHP Cell And Exploration For The Mechanism Of Resistance

Objective:To establish an oxaliplatin (L-OHP)-resistant human gastric carcinomaSGC-7901/L-OHP cell and to explorate its mechanism of resistance.Methods:Oxaliplatin-resistant SGC-7901/L-OHP cells were established by gradually increasingthe concentration of L-OHP. The sensibility of diverse medicines in SGC-7901andSGC-7901/L-OHP cells were detected by MTT assay. The changes of cell cycle weredetected by FCM (flow cytometry). The expressions of resistance-associated genes andprotein were determined by RT-PCR and Western Blot Analysis.Results:The SGC-7901/L-OHP cells with stable resistance were successfully established.Thecell doubling time of SGC-7901/L-OHP cells(36.18h)is longer than SGC-7901cells(31.84h).Cells in the G0/G1phase of the cell cycle increased, while in the G2/M phasedecreased, cell Proliferation Index increased(P<0.05).The SGC-7901/L-OHP cells hadcross-resistance with L-OHP, cisplatin， fluorouracil, docetaxel and octreotide. Theexpression levels of P-gp, GST, MRP and Bcl were higher in SGC-7901/L-OHP cells thanthose in SGC-7901cells (P<0.01), while the expression level of Bax was lower inSGC-7901/L-OHP cells than those in SGC-7901cells.Conclusion:The SGC-7901/L-OHP cells obtain stable resistance of L-OHP and had cross-resistance with L-OHP, octreotide, fluorouracil, docetaxel and octreotide. Themechanism of SGC-7901/L-OHP cells may be related with the up-regulation and down-regulation of resistance associated protein expression.