In:
Anti-Cancer Agents in Medicinal Chemistry, Bentham Science Publishers Ltd., Vol. 22, No. 18 ( 2022-11), p. 3107-3113
Abstract:
This study is part of a larger research effort to explore the molecular mechanism of hepatocellular
carcinoma, reduce drug resistance and seek new targets. Objective: The objective of this study is to investigate the effect and mechanism of fibroblast growth factor receptor
inhibitor AZD4547 on Sorafenib-resistant hepatoma cells. Methods: First, we constructed a Sorafenib-resistant hepatoma cell line Huh7R. Different groups of Huh7R cells were
treated with Sorafenib, AZD4547, Sorafenib combined with AZD4547, and normal saline. The cell viability was detected by Cell Counting Kit-8. Then Fibroblast growth factor receptor and Toll-like receptor 4 were detected by Western
blot, as well as the LC3 II/I, Beclin1, and P62. In addition, we used the autophagy inhibitor 3-methyladenine to identify the mechanism of AZD4547 combined with Sorafenib for inducing Sorafenib-resistant hepatoma cell death. Results: We find that AZD4547 combined with Sorafenib significantly inhibited the viability of Sorafenib-resistant
hepatoma cell Huh7R. As for its mechanism, AZD4547 was able to inhibit fibroblast growth factor receptor activity, promote autophagy and regulate immunity. AZD4547 increased LC3 II/I, Beclin1, and Toll-like receptor 4 proteins,
and decreased P62 protein level in Huh7R cells significantly when given in combination with sorafenib. Furthermore, 3-methyladenine inhibited autophagy and reversed the killing effect of the combination of AZD4547 and Sorafenib on
Huh7R cells. Conclusion: The inhibition of fibroblast growth factor receptor activity by AZD4547 can significantly enhance autophagy
and immune response, as well as promote the death of Sorafenib-resistant hepatoma cells.
Type of Medium:
Online Resource
ISSN:
1871-5206
DOI:
10.2174/1871520622666220425124419
Language:
English
Publisher:
Bentham Science Publishers Ltd.
Publication Date:
2022
SSG:
15,3
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