Effects of multi-target tyrosine kinase inhibitor Acitinib on liver fibrosis
- VernacularTitle:多靶点酪氨酸激酶抑制剂阿西替尼治疗肝纤维化的作用与机制
- Author:
Sinan LIU
1
;
Zichao HUANG
2
;
Wenchao BI
3
;
Ruixia CUI
1
;
Kai QU
1
;
Chang LIU
1
Author Information
- Publication Type:Journal Article
- Keywords: liver fibrosis; hepatic stellate cell; Axitinib; tyrosine kinase inhibitor
- From: Journal of Xi'an Jiaotong University(Medical Sciences) 2021;42(4):508-514
- CountryChina
- Language:Chinese
-
Abstract:
【Objective】 To observe the therapeutic effects of Axitinib, a tyrosine kinase receptor inhibitor, on liver fibrosis. 【Methods】 In vivo, CCL
4 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.
