To Explore The Effect And Mechanism Of TLR4/Nanog/ABCF2 Pathway In Reversing Platinum Resistance Of Gastric Cancer Cells By Polyene Phosphatidylcholine In The Nude Mouse Model

Objective: To investigate the mechanism of the reversal resistance of polyene phosphatidylcholine to human gastric cancer-resistant oxaliplatin cell line(SGC-7901/LOHP)in the nude mouse model.Methods: The nude mouse models of subcutaneous xenograft were established by secondary drug-resistant cell line(SGC-7901/L-OHP)and randomly divided into 4 groups,including blank control group,polyene phosphatidylcholine(PPC)group,The oxaliplatin(L-OHP)group and the oxaliplatin combined with the polyene phosphatidylcholine(L-OHP+PPC)group.The 4 groups were administered continuously for 14 days.After 21 days,the nude mice were sacrificed,the tumor tissues were dissected and its volume and inhibition rate were recorded.The RNA and protein of the tumor tissues were extracted from the excised tumor tissues.TLR4、 Nanog and ABCF2 expression levels were observed by use methods of real-time quantitative PCR(qRT-PCR)and Western blot.Results: Compared with the blank control group the proliferation of transplanted tumor cells in L-OHP group and L-OHP+PPC group was inhibited,P <0.001.The combination of the two drugs had an interaction effect,P =0.008.The volume inhibition rate of L-OHP+PPC group was higher than that of the blank control group(P <0.001)and L-OHP group(P <0.001).The mRNA expression of TLR4/Nanog/ABCF2 in L-OHP+PPC group was significantly different from that in the control group(TLR4 P <0.001;Nanog P <0.001;ABCF2 P <0.001);the mRNA expression of TLR4/ Nanog / ABCF2 in the L-OHP+PPC group was significantly different from that of L-OHP group(TLR4 P <0.001;Nanog P <0.001;ABCF2 P <0.001).There was an interaction between the two drugs which may influence the expression of TLR4/Nanog/ABCF2 mRNA(TLR4 P <0.001;Nanog P<0.001;ABCF2 P<0.001).The protein expression of TLR4/Nanog/ABCF2 in L-OHP+PPC group was significantly different from that in the control group(TLR4 P =0.006;Nanog P =0.017;ABCF2 P =0.014);the protein expression of TLR4/Nanog/ABCF2 of the L-OHP+PPC group was significantly different from that of L-OHP group(TLR4 P <0.001;Nanog P <0.001;ABCF2 P <0.001).The combination of the two drugs had an interaction effect on the protein expression of TLR4/Nanog/ABCF2,and the difference was statistically significant(TLR4 P =0.014;Nanog P =0.01;ABCF2 P =0.015).Conclusion:Polyene phosphatidylcholine can reverse the drug resistance in human gastric cancer-resistant oxaliplatin cell line(SGC-7901/L-OHP)in nude mice,possibly by influencing the expression Of TLR4,Nanog and ABCF2 in those cells.