Evaluation of Ameliorative Efficacy of Carboplatin with Pioglitazone Through Adiponectin Augmentation by Activating PPAR-γ in High-Fat Diet-Induced Ovarian Cancer in Mice

Abstract Carboplatin is one of the preferred treatments for ovarian cancer. To improve the therapeutic effectiveness of carboplatin in ovarian cancer, the novel combination therapy of carboplatin with the peroxisome proliferator-activated receptor-gamma agonist pioglitazone was studied in a high-fat diet-induced ovarian cancer model. Thirty Swiss Albino mice (20-35 g) were randomly divided into five groups. Group I received a regular diet, while groups II-V were fed a high-fat diet, with group II serving as the disease control. Groups III-V received carboplatin (133 mg/kg), carboplatin (133 mg/kg) plus pioglitazone (3 mg/kg), and carboplatin (133 mg/kg) plus pioglitazone (9 mg/kg), respectively, for 14 weeks. On day 56 of the study, cancer induction was confirmed by measuring serum lipid profile, pro-inflammatory cytokines, and adiponectin levels. Following this, drug treatment was administered for 6 weeks. On day 98, treatment efficacy was evaluated through serum lipid profiles and pro-inflammatory cytokine levels, and confirmed by ovarian histological studies. The combination therapy of carboplatin and pioglitazone significantly altered serum lipid profiles (TC, TG, LDL, and HDL) and pro-inflammatory cytokine (IL-6, TNF-α, and MCP-1) levels. Additionally, it increased adiponectin levels by activating the PPAR-γ receptor, compared to the disease control. The combination of carboplatin with the PPAR-γ activating ligand pioglitazone enhances the efficacy of carboplatin in ovarian carcinoma by increasing plasma adiponectin levels, which effectively reduces cytokines and chemokines responsible for tumor progression in obesity-induced ovarian cancer.