Effects of "Zengmian Yiliu Decoction" on expression of resistance related genes HIF-1α,Glut1,MDR1,P-gp in nude mice with Cisplatin-resistant ovarian cancer

Objective To study the effect of Zengmian Yiliu Decoction on expression of resistance related genes HIF-1α,Glut1,MDR1 and P-gp in nude mice with Cisplatin-resistant ovarian cancer.Methods Using the cisplatin resistant ovarian cancer cell line COC1/DDP to build the model of ovarian cancer subcutaneous tumor in nude mice.The mice were randomized into six groups: control group,herb groups(high,medium and low dose),cisplatin group(DDP) and combined group(DDP combined with herbs),intervened with for three weeks,measured the maximum and minimum tumor diameter on a regular basis,making the tumor growth curve.After administration,mice were sacrificed to measure the tumor weight and calculate inhibition rate,determining the expression of HIF-1α and Glut1 by immunohistochemical method,to determine the expression of MDR1 and P-gp by Quantitative RT-PCR.Results ①Inhibition rate: The inhibition rate in combined group was highest,(59.26±6.86)%,compared with other groups,there was a significant difference(P0.01).There was certain inhibitory effect in each herb group,but inhibition rate was lower than cisplatin group(P0.01).②Immunohistochemical results: The expression of HIF-1α in combined group was lowest(P0.01);expression of HIF-1α reduced in herb high and medium dose groups compared with cisplatin group(P0.01);low dose group with no significant difference(P0.05).The expressions of Glut1 in combined group and herb high dose group were lower than that in cisplatin group(P0.01);there was no significant difference between medium dose group and cisplatin group(P0.05);low-dose group was higher than cisplatin group(P0.05),but compared with the control group there was no significant difference(P0.05).③Quantitative RT-PCR results: The expressions of MDR1 and P-gp in cisplatin group were higher than that in control group(P0.01);the expressions of MDR1 and P-gp in combined group and herb groups were lower than that in cisplatin group(P0.01).Conclusion Zengmian Yiliu Decoction with chemotherapy can reverse the cisplatin-resistance in nude mice with resistant ovarian cancer,and enhance its inhibitory effect.The mechanism is to down regulate the expressions of MDR1 and P-gp by down regulating the expressions of Glut1 and HIF-1α to improve the chemotherapy-resistance in ovarian cancer from hypoxia-mediated drug pump mechanism.