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Purpose: To determine the efficacy of Lycium barbarum polysaccharide (LBP) in ovarian cancer, and the synergistic effect when used in combination with paclitaxel/cisplatin (PXT∕DDP).
Methods: ID-8 cells were injected subcutaneously into 5 groups of female C57BL/6 mice (5 mice/group): control (Con), chemotherapy (CH, PTX/DDP), combination therapy 1 (co-CH1, PTX/DDP + 50 mg/kg LBP), combination therapy 2 (co-CH2, 100 mg/kg LBP) and combination therapy 3 (co-CH3, 150 mg/kg LBP). Tissue morphological changes were monitored by hematoxylin and eosin (H&E) staining. Protein and mRNA levels of Keap1, Nrf2) and heme oxygenase-1 (HemO-1) were analyzed by western blotting and real-time polymerase chain reaction (PCR), as applicable.
Results: Growth rate and volume of tumors were significantly reduced in the chemotherapy and combination therapy groups, while organ index increased significantly in co-CH group. Morphological structure of tumor, liver and kidney became normal after combination therapy. Levels of alanine transaminase (ALT), aspartate transaminase (AST), alkaline phosphatase (ALP), uric acid (UA), creatinine (Cr) and blood urea nitrogen (BUN) were significantly decreased in co-CH group relative to CH group. Lymphocytes, monocytes (MNC), neutrophils, basophils and eosnophils were significantly regulated by combination therapy. In CH and co-CH1-3 groups, the mRNA and protein levels of Keap1, HO-1 and Nrf2 were significantly increased relative to those of control mice.
Conclusion: LBP in combination with PXT∕DDP enhances the efficacy of the latter, and reduced its toxicity when used for the treatment of ovarian malignant tumor in mice, by activating Keap1/Nrf2 pathway and promoting immunity.
Keywords: Lycium barbarum polysaccharide (LBP), Paclitaxel/Cisplatin, Keap1/Nrf2 pathway, Cytotoxicity