WITHDRAWN: The role of Apatinib combined with Paclitaxel (aluminum binding type) in drug-resistant ovarian cancer

Abstract

ObjectiveTo assess the antitumor effects and side reactions of different dosages of Paclitaxel (albumin binding) combined with Apatinib in drug-resistant ovarian cancer cell line and xenotransplantation tumor model. MethodsConventional cell experiments were used to evaluate the effects of Apatinib and Paclitaxel (albumin binding), SKOV-3/DDP were selected as research object and divided into 3 groups for study, a): control group, no drug intervention; b): nab-P group, Paclitaxel (albumin binding type) 40 µmol/l; c): Apatinib group, Apatinib 50 µmol/l. The IC-50 value of the drug was detected by MTT test, apoptosis related protein(Bax, bcl-2), vascular related protein(p-VEGFR-2), invasion related protein(MMP-2) expression were detected by Western blot and Cellular immunofluorescence, the invasion and migration ability of tumor cells were detected by Transwell and Cell scratch test. Based on these dates, establishing different dosages of Paclitaxel (albumin binding type) combined with Apatinib, a): Control group, no drug intervention; b): Group-1, Paclitaxel (albumin binding type) 5 µmol/l + Apatinib 10 µmol/l, c): Group-2, Paclitaxel (albumin binding type) 4.5 µmol/l + Apatinib 10 µmol/l, d): Group-3, Paclitaxel (albumin binding type)4 µmol/l + Apatinib 10 µmol/l, the index of combined use was analyzed by Compusyn software, Western blot, Immunofluescence, Transwell, Cell scratch test also were chose to change of inhibition effect. On the other hand, we used xenograft tumor model to verify the results in vivo. BALB/c female nude mice were randomly divided into 4 groups, a): Control group, no drug intervention; b): Paclitaxel (albumin binding type) 20 mg/kg + Apatinib 150 mg/kg, c): Paclitaxel (albumin binding type) 18 mg/kg + Apatinib 150 mg/kg, d): Paclitaxel (albumin binding type) 16 mg/kg + Apatinib 150 mg/kg. The tumor growth curve was analyzed during the test. The apoptosis related protein (Bax, bcl-2), angiogenesis related protein (CD31, p-VEGFR-2) and invasion related protein(MMP-2) were analyzed by Western blot, Immunofluescence and Immunohistochemistry to analysis the effect of antitumor and side reactions Result (1) The IC-50 value of SKOV-3/DDP to paclitaxel (albumin binding type) was 45.53 ± 4.06 µmol/l, while