Search

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. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate the role of signal transducer and activator of transcription 3 (STAT3) and mucin 1(MUC1) in non-small cell lung carcinoma (NSCLC) and the use of their inhibitors to reduce chemoresistance. Methods: Cisplatin or vinblastine was provided either with or without STAT3 inhibitor and evaluated for chemoresistance in NSCLC cells and a xenograft mice tumor model. Immunohistochemistry and Kaplan-Meier method of survival analysis were used to determine chemoresistance trends in patients. STAT3 inhibitor treatment, RNAi or ectopic overexpression of STAT3 or MUC1 in NSCLC cells were used to determine their inter-molecular relation and for modulating stemness-related genes. Results: A major subset of chemoresistance patients exhibited a combined aberration of both STAT3 and MUC1 and exhibited a significantly reduced median overall survival (p = 0.008). Subsequent in vitro experiments in NSCLC cells showed that STAT3 levels modulate MUC1 expression (p < 0.01) and increase stemness gene expressions such as AKT (3-fold), OCT4 (4-fold), SOX2 (2-fold) and CXCR4 levels (2-fold). In addition, co-treatment of STAT3 inhibitor with cisplatin or vinblastine enhanced drug efficiency in viability and invasion assays (p < 0.01) and in a xenograft mouse model (p < 0.05). Conclusion: STAT3 inhibitor co-treatment with chemotherapy drugs increases drug efficacy and reduced tumor growth, and therefore, may improve outcomes in patients on NSCLC chemotherapies. [ABSTRACT FROM AUTHOR]