Attenuation and synergism of Hugan buzure recipe combined with oxaliplatin on hepatocellular carcinoma tumor bearing nude mice and its mechanism / 中国药房

ABSTRACT

OBJECTIVE To investigate the attenuation and synergism of Hugan buzure recipe （HBR） combined with oxaliplatin on hepatocellular carcinoma tumor bearing nude mice and its mechanism. METHODS Eight nude mice were selected from 40 nude mice as the blank group （normal saline）， and the remaining nude mice were inoculated with hepatoma cells Huh7 to establish the tumor-bearing model. The 32 modeled nude mice were randomly allocated to four groups： model group （normal saline， ig）， HBR group （0.69 g/kg， ig）， oxaliplatin group （10 mg/kg， ip）， and combination group （intraperitoneal injection of 0.69 g/kg HBR+intragastric administration of 10 mg/kg oxaliplatin）， with 8 mice in each group. Administer drug/normal saline once a day for 32 consecutive days； administer subcutaneous injection once every 7 days for a total of 5 times. During the experiment， the general condition of nude mice in each group was observed， and the tumor volume was measured every 4 days. On the 30th day of administration， the thermal stimulation paw withdrawal latency of nude mice in each group were detected. The tumor inhibition rate， spleen coefficient， the number of red blood cells， white blood cells and platelets in the whole blood of nude mice in each group， and the content of aspartate aminotransferase （AST） and creatinine in serum were detected after the end of administration. HE staining was used to observe the pathological changes in tumor tissues in nude mice in each group. The expression of microtubule-associated protein 1 light chain 3 （LC3），selective autophagy adaptor protein p62， B-cell lymphoma-2 （Bcl-2）， Bcl-2 associated X protein （Bax）， and Caspase-3 protein in tumor tissues. RESULT Compared with the model group， the tumor volume， tumor weight， white blood cells，red blood cells in the whole blood and spleen coefficients of nude mice in the oxaliplatin group were significantly decreased （P＜0.01）； the thermal stimulation paw withdrawal latency， AST and creatinine in serum were significantly increased （P＜0.05 or P＜0.01）. Compared with the oxaliplatin group， the tumor volume and tumor weight of nude mice in the combination group were significantly decreased （P＜0.01）； the white blood cells， red blood cells and platelets in the whole blood and spleen coefficients of nude mice were significantly increased （P＜0.05 or P＜0.01）； the thermal stimulation paw withdrawal latency， AST and creatinine in serum were significantly decreased （P＜0.01）； the expression levels of LC3， Bax and Caspase-3 proteins in tumor tissues of nude mice were significantly increased （P＜0.01）， and the expression levels of p62 and Bcl-2 proteins were significantly decreased （P＜0.01）. CONCLUSIONS HBR enhances the tumor inhibition rate of oxaliplatin by inducing apoptosis and autophagy， and can alleviate the peripheral neurotoxicity， hematological toxicity， hepatorenal toxicity， and immune organ toxicity caused by oxaliplatin in nude mice.