Effect of simplified formula of Jinfukang Oral Liquid on apoptosis of renal tubular epithelial cells induced by cisplatin
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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