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1.
Journal of Xi'an Jiaotong University(Medical Sciences) ; (6): 508-514, 2021.
Artículo en Chino | WPRIM | ID: wpr-1006682

RESUMEN

【Objective】 To observe the therapeutic effects of Axitinib, a tyrosine kinase receptor inhibitor, on liver fibrosis. 【Methods】 In vivo, CCL4 was injected intraperitoneally to induce liver fibrosis in mice. After modeling, Axitinib-carboxymethyl cellulose (Axitinib-CMC) solution or CMC solution were administered by gavage. After 2 weeks of modeling, 4 weeks of modeling, 1 week of treatment and 2 weeks of treatment, the mice were killed and their liver tissues were stained by HE, Masson and α - SMA immunohistochemistry. In vitro, human hepatic stellate cell line (LX2) and human normal liver cell line (LO2) were intervened with different concentrations of Axitinib-CMC solution. MTT assay was performed 48 h and 72 h after the intervention. Flow cytometry was used to observe the apoptosis of the two cell lines. Western blotting was used to detect the expressions of Fas, Caspase-8, Caspase-3 and Bcl-2 proteins. 【Results】 HE and Masson staining results showed that CCL4 could induce liver fibrosis in the mice, and the degree of liver fibrosis was more severe in the 4-week than that in the 2-week treatment group. After treatment with Axitinib, the collagen staining area and the positive expression level of α-SMA were significantly lower than those in 4-week group and CMC treatment control group (P<0.05). In vitro, Axitinib could effectively inhibit the viability of hepatic stellate cell line LX2 and promote its apoptosis. Meanwhile, the expressions of pro-apoptotic proteins Fas, Caspase-8 and Caspase-3 increased, while the expression of apoptosis suppressor gene Bcl-2 decreased. However, the above changes were not found in control hepatocyte line LO2. 【Conclusion】 Axitinib exerts an anti-fibrosis effect by inducing apoptosis of hepatic stellate cells, and has no significant effect on normal hepatocytes.

2.
Journal of Southern Medical University ; (12): 1253-1259, 2013.
Artículo en Inglés | WPRIM | ID: wpr-319433

RESUMEN

<p><b>OBJECTIVE</b>Cellular senescence as one of the important steps against tumor is observed in many cancer patients receiving chemotherapy and is related to chemotherapeutic response. To investigate the effect of cisplatin on hepatocellular carcinoma, we treated HepG2 cells exhibiting wild-type TP53 with gradient concentrations of cisplatin.</p><p><b>METHODS</b>The inhibitory effects of cisplatin on human hepatoma HepG2 cells were detected by MTT assay and colony formation test. The changes in cell cycle were analyzed by flow cytometry, and cellular senescence was detected with senescence associated β-galactosidase (SA β-gal) staining. The relative mRNA expression levels of TP53, P21 and P19 was estimated using semi-quantitative real-time RT-PCR, and the protein expressions of P53 and P21 were detected using Western blotting.</p><p><b>RESULTS</b>Cisplatin induced irreversible proliferation inhibition and G1 phase arrest of HepG2 cells. Elevated levels of senescence-associated β-galactosidase was observed in HepG2 cells exposed to low doses of cisplatin. P19 expression immediately increased following cisplatin exposure and reached the maximum level at 48 h, followed then by a rapid decrease to the baseline level, whereas the expressions levels of TP53 and P21 mRNA increased continuously. Western blotting confirmed P53 and P21 expression changes similar to their mRNA expressions during cisplatin-induced cellular senescence in HepG2 cells.</p><p><b>CONCLUSION</b>Our results revealed a functional link between cisplatin and hepatocellular senescence. Cellular senescence induced by cisplatin as a stabile senescent cellular model can be used for further research.</p>


Asunto(s)
Humanos , Ciclo Celular , Puntos de Control del Ciclo Celular , Senescencia Celular , Cisplatino , Farmacología , Inhibidor p19 de las Quinasas Dependientes de la Ciclina , Metabolismo , Inhibidor p21 de las Quinasas Dependientes de la Ciclina , Metabolismo , Células Hep G2 , Proteína p53 Supresora de Tumor , Metabolismo , Regulación hacia Arriba
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