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OBJECTIVE To investigate the improvement mechanism of caudatin on liver injury of rats. METHODS SD rats were randomly divided into blank group， model group， caudatin low-dose and high-dose groups （25， 50 mg/kg）， with 6 rats in each group. Diethylnitrosamine （DEN） was injected intraperitoneally three times per week for eight weeks to establish liver injury model of rats. At 5th week of modeling， the rats received relevant medicine or 0.5% sodium carboxymethylcellulose intragastrically for 4 weeks. The levels of liver function indexes [alanine transaminase （ALT）， aspartate transaminase （AST）， total protein （TP） and total bilirubin （TBI）] and inflammatory factors [interleukin （IL-6）， tumor necrosis factor α （TNF-α）， IL-1β] in serum were detected； the histopathological morphological changes of rat liver were observed； the positive protein expressions of nuclear factor κB （NF-κB） and 78 kDa glucose regulatory protein （Grp78） in liver tissue were also determined； the expressions of endoplasmic reticulum stress-related protein Grp78， C/EBP homologous protein （CHOP）， activating transcription factor 6 （ATF6） and inositol requiring enzyme 1α （IRE1α） and the level of protein kinase R-like endoplasmic reticulum kinase robertluoyi@126.com （PERK） in liver tissue were detected. RESULTS Compared with blank group， serum levels of ALT， AST， TBI， IL-6， TNF-α and IL-1β and positive expressions of NF-κB and Grp78 in liver tissue as well as protein expressions of Grp78， CHOP， ATF6 and IRE1α， PERK protein phosphorylation level were all increased significantly in model group （P＜0.05）， while the serum level of TP was decreased significantly （P＜0.05）. The disordered structure of liver lobule， swollen liver cells， unclear intercellular boundary were observed and accompanied by inflammatory cell infiltration. Compared with model group， most of the above indexes were significantly reversed in caudatin groups （P＜0.05）； the structure of hepatic lobule was relatively complete and clear， the cells were arranged orderly， and the infiltration of inflammatory cells was also reduced. CONCLUSIONS Caudatin has a significant improvement effect against DEN-induced liver injury in rats， the mechanism of which may be associated with inhibiting endoplasmic reticulum stress and inflammatory reaction.
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Objective To investigate the effect and underlying mechanism of Caudatin combined with Gefitinib on Gefitinib resistance induced by HGF in PC-9.Methods Model of EGFR-TKIs resistance in PC-9 cells was induced by exogenous HGF and co-cultured with MRC-5.Caudatin was tested as a drug resistant modulator to reverse the resistance of Gefitinib in PC-9 cells induced by HGF by MTT assay.Western blot was performed to observe the mechanism of Caudatin combined with Gefitinib reversing the resistance of PC-9 induced by HGF.Results The resistance of gefitinib to PC-9 was induced by exogenous HGF and co-cultured with MRC-5 which could reduce relative inhibitory rate ( P<0.05 ) .Neither caudatin ( 0-32 μM ) or Gefitinib (1μM) alone could significantly inhibit proliferation of PC-9 in the presence of HGF, which could be inhibited in a dose-dependent manner by Caudatin combined with Gefitinib ( P<0.05 ); Caudatin combined with Gefitinib down-regulated the phosphorylation levels of Met and PI3K/Akt simultaneously (P<0.05).Conclusion Caudatin could reverse the drug resistance of Gefitinib in PC-9 induced by HGF, the mechanism of which may be related to the inhibition of Met/PI3K/AKT pathway.
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AIM:To determine whether caudatin , a C21 steroidal aglycone , enhances tumor necrosis factor-re-lated apoptosis-inducing ligand ( TRAIL)-associated HepG2 cell apoptosis .METHODS:Cell growth inhibition was deter-mined by MTT assay and cell colony formation assay .The TUNEL apoptosis detection kit was used to analyze cell apopto-sis, and the protein expression was examined by Western blotting .RESULTS:Combination of caudatin with TRAIL signi-ficantly reduced cell proliferation and increased the apoptotic rate of HepG 2 cells compared with the use of each agent alone.This was evidenced by marked increases in caspase-3, caspase-7, caspase-9 and PARP cleavages in the cells treated with caudatin and TRAIL-compared with control group .Combination of caudatin with TRAIL also led to the strong suppres-sion of survivin .CONCLUSION:Caudatin synergizes HepG 2 cells to TRAIL-induced apoptosis by promoting the cleava-ges of caspase-3, caspase-7, caspase-9 and PARP and inhibiting the expression of survivin .
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Objective: To investigate the effects of Caudatin on cell proliferation and migration of human glioma cell line C6 and the potential mechanisms. Methods: Cell viability was evaluated by MTT assay. Cell cycle distribution was assessed by propidium iodide flow cytometry. Scarification test and Transwell assay were used to measure the cell migration. The effects of Caudatin on the expression of β-catenin, Survivin, CyclinD1, and Cdk4 were determined by Western blotting assay. Results: Caudatin inhibited the C6 cell viability in a dose dependent manner, and caused an accumulation of C6 cells in G1 phase, and Western blotting results suggested that Caudatin inhibited the expression of CyclinD1 and Cdk4. The migration ability of C6 cells was significantly blocked by Caudatin treatment. Caudatin could significantly down-regulate the expression of β-catenin and Survivin in C6 cells. Conclusion: Caudatin could inhibit the C6 cell migration in vitro with a dose dependent way, and the potential mechanism might be related to inhibiting the expression of β-catenin and Survivin in C6 cells.