Establishment Of Xenograft Models Of Drug-Resistant Ovarian Carcinoma In Nude Mice

Objective: Multidrug resistance (MDR) is a phenomenon that cancer cells develop a cross-resistant phenotype against several unrelated drugs that differ widely with respect to molecular structure and target specificity, which is a serious obstacle to chemotherapy in ovarian cancers. Overexpression of MDR1, a member of the ABC (ATP-binding cassette) transporters, has been directly implicated in resistance to a broad spectrum of chemotherapeutic reagents. Consequently, it is necessary to develop less toxic and more efficient strategies to overcome MDR. However, there are little animal models for us to use at present. This study was created to establish xenograft models of drug-resistant ovarian carcinoma in nude mice , and to explore the biological characteristics and mechanism of multidrug resistance, which can provide an ideal animal model for the basic, and clinical study of MDR.Methods: Nude mice were divided into 2 groups at random: group induced in vitro and group induced in vivo. Then group induced in vitro were subdivided into group I and II, and group induced in vivo into group III and IV respectively. The OVCAR/AR cells were injected subcutaneously in group I , and the OVCAR-3 cells were injected the same site in group II as a control. When the volume of tumor reached 100 mm3, Chemotherapeutics was injected veinously with a single dose of 20mg/kg. Mice in group I and II were sacrificed 21 days after chemotherapy. The OVCAR-3 cells were injected subcutaneously both group III and IV. When the volume of tumor reached 100 mm3, Adriamycin (0.65mg/kg) was injected subcutaneously around the tumor each day in group III, while physiologic saline was injected in group IV as a control. Mice in groupIII and IV were sacarificed 8 weeks after drug inducing. The volumes of the tumors were measured and the tumor growth rates were calculated. The tumors were examined by immunohistochemistry and RT-PCR.Results: All nude mice were successfully inoculated and all induced tumors developed. The pathological morphological observation indicated xenografts with malignant phenotype. The volume of tumor and growth rate in group I were both higher than group II (P<0.05). The expression levels of MDR1 mRNA and P-gp in group I were significantly higher than that in group II respectively (P<0.05). The volume of tumor in group IV were higher than group III(P<0.05). The expression levels of MDRl mRNA and P-gp in group III were both significantly higher than that in group IV(P<0.05).Conclusions: Our study showed MDR phenotype was elevated obviously in both groups induced in vitro and in vivo. Xenograft models of drug-resistant ovarian carcinoma in nude mice provide a good way for studying the mechanism of MDR and investigating the methods to reverse MDR.