Effect And Mechanism Of EGb761 Reversing NF-?B-mediated Drug Resistance In Gastric Cancer Cells

OBJECTIVE:To investigate the effect of Ginkgo biloba extract(EGb761)on the proliferation and apoptosis induced by cisplatin in gastric cancer SGC-7901 and SGC-7901/CDDP cells and to explore the chemotherapy resistance mechanism of gastric cancer cells.METHODS:The experiment is divided into SGC-7901 and SGC-7901/CDDP two groups,SGC-7901 and SGC-7901/CDDP cells were treated with EGb761,cisplatin or EGb761 combined with cisplatin.Cell proliferation activity was measured by MTT assay and apoptosis was measured by flow cytometry.The m RNA expression of NIBP and NF-?B p65 was detected by real-time PCR,the protein expression of NIBP and NF-?B p65 was analyzed by Western blot.RESULTS:Monotherapy with EGb761 and cisplatin significantly inhibited the growth of SGC-790 l and SGC-7901/CDDP cells in a dose-dependent manner,but SGC-7901/CDDP cells were less sensitivity to cisplatin.EGb761 significantly enhanced the inhibitory effect of cisplatin on cell growth.Cells treated with EGb761 combined with cisplatin showed a significantly higher level ofapoptosis than treated with cisplatin alone.The mRNA and protein expression levels of NIBP and NF-?B p65 in SGC-7901/CDDP cells were relatively higher than those of SGC-7901 cells(P<0.05).EGb761 significantly inhibited cisplatin-induced NF-?B p65 and NIBP the expression(P<0.05).Follows were the detailed results,the m RNA expression of NIBP in CON + SGC-7901 group(1.065±0.039)vs CON + SGC-7901/CDDP group(1.606±0.065)and EGb761+ SGC-7901 group(0.899±0.036)vs EGb761 + SGC-7901/CDDP group(1.363± 0.067)and DDP + SGC-7901 group(1.444 ± 0.058)vs DDP +SGC-7901/CDDP group(2.356±0.092)and EGb761 + DDP + SGC-7901 group(1.107±0.040)vs EGb761 + DDP + SGC-7901/CDDP group(1.780±0.076).The m RNA expression of NF-?B p65 in CON + SGC-7901 group(1.115±0.036)vs CON + SGC-7901/CDDP group(1.442±0.025)and EGb761 + SGC-7901group(0.857±0.087)vs EGb761 + SGC-7901/CDDP group(1.206±0.071)and DDP + SGC-7901 group(1.480 ± 0.148)vs DDP + SGC-7901/CDDP group(2.619 ± 0.215)and EGb761 + DDP + SGC-7901 group(1.148 ± 0.056)vs EGb761 + DDP + SGC-7901/CDDP group(1.634 ± 0.072).The protein expression of NIBP in CON + SGC-7901 group(0.324 ± 0.021)vs CON +SGC-7901/CDDP group(0.707±0.037)and EGb761 + SGC-7901 group(0.233± 0.023)vs EGb761 + SGC-7901/CDDP group(0.591 ± 0.037)and DDP +SGC-7901 group(0.590±0.023)vs DDP + SGC-7901/CDDP group(0.990±0.037)and EGb761 + DDP + SGC-7901 group(0.328±0.022)vs EGb761 +DDP + SGC-7901/CDDP group(0.725 ± 0.037).The protein expression of NF-?B p65 in CON + SGC-7901 group(0.783 ± 0.029)vs CON +SGC-7901/CDDP group(1.540±0.038)and EGb761 + SGC-7901 group(0.628± 0.030)vs EGb761 + SGC-7901/CDDP group(0.865 ± 0.031)and DDP +SGC-7901 group(1.138±0.029)vs DDP + SGC-7901/CDDP group(1.981±0.030)and EGb761 + DDP + SGC-7901 group(0.770±0.028)vs EGb761 +DDP + SGC-7901/CDDP group(1.508±0.016).CONCLUSION:EGb761 may be able to reverse the drug resistance of gastric cancer cells.Its chemotherapy sensitizing effect may be achieved by inhibiting the activity of NF-?B pathway and the expression of NIBP.