In order to study the effect of the simplified formula of Jinfukang Oral Liquid(ALG-12)on renal tubular injury induced by cisplatin(DDP),48 C57 mice were divided into control group,model group,DDP group,and DDP combined with low,medium,and high dose groups of ALG-12.The mice were administered for 16 days after the establishment of the subcutaneous Lewis lung cancer heterotopic transplant tumor model of mice.The pathological changes,serum creatinine(Scr),blood urea nitrogen(BUN),kidney injury molecule 1(Kim-1),neutrophil gelatinase-associated lipocalin(NGAL),malondialdehyde(MDA),and total superoxide dismutase(T-SOD)in renal tissue and the degree of renal tubular cell apoptosis were analyzed to investigate the effect of ALG-12 on renal injury induced by DDP treatment on non-small cell lung cancer(NSCLC).The human renal cortex proximal tubule epithelial cell(HK-2)model was constructed in vitro,and the effect of ALG-12 drug-containing serum on HK-2 cytotoxicity of DDP was evaluated by CCK-8,cell cycle,and apoptosis tests.Real-time quantitative reverse transcription PCR(RT-qPCR),Western blot,and immunohistochemistry were used to analyze the expression levels of tumor protein p53-mediated apoptosis-related genes by ALG-12.The results showed that ALG-12 could significantly reduce the abnormalities of biochemical indexes like Scr,BUN,Kim-1,NGAL,MDA,and T-SOD and decrease the degree of renal tubular injury,renal interstitial fibrosis,and renal cell apoptosis,suggesting that ALG-12 could reduce the renal injury induced by DDP in vivo.In vitro cell assay found that ALG-12 containing serum could inhibit apoptosis and cell cycle arrest induced by DDP in HK-2 cells.In addition,ALG-12 inhibited the transcription of ataxia-telangiectasia mutated-and Rad3-related gene(ATR),tumor protein p53 gene(Tp53),Bcl-2 binding component 3 gene(BBC3),and Bcl-2 associated X protein gene(Bax)in the p53 signaling pathway,decreased the protein expression levels of p53,Bax,and cleaved caspase-3,and increased the protein expression levels of B-cell lymphoma/leukemia 2(Bcl-2)and caspase-3.The results suggested that ALG-12 had a protective effect on DDP-induced renal tubular epithelial cell injury,and the mechanism may be related to the inhibition of p53-mediated apoptosis,which provided a basis for further development of ALG-12.
simplified formula of Jinfukang Oral Liquidcisplatinrenal tubular injurynon-small cell lung cancerapoptosis
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