Inhibition and Mechanism of Imatinib on A549 Xenograft Tumor in Nude Mice via PDGF/PDGFR Pathway
10.3971/j.issn.1000-8578.2023.23.0228
- VernacularTitle:伊马替尼通过PDGF/PDGFR通路对A549非小细胞肺癌裸鼠移植瘤的抑制作用及机制研究
- Author:
Bingtian XIA
1
;
Fang HE
;
Bingxin SONG
;
Lili WANG
;
Tingjun ZHU
;
Yongqing JIA
;
Huixian HU
Author Information
1. Department of Hematology, The Affiliated Jinhua Hospital, Zhejiang University School of Medicine, Jinhua 321000, China
- Publication Type:Research Article
- Keywords:
Non-small cell lung cancer;
Imatinib;
Platelet-derived growth factor;
Platelet-derived growth factor receptor
- From:
Cancer Research on Prevention and Treatment
2023;50(9):854-859
- CountryChina
- Language:Chinese
-
Abstract:
Objective To investigate the effect of imatinib on the growth of A549 non-small cell lung cancer transplanted tumors and the expression of PDGFB and PDGFRβ proteins in tumor tissues and stroma in nude mice and to explore the underlying tumor suppression mechanism. Methods A transplantation tumor model of A549 non-small cell lung cancer was established in nude mice. The mice were then randomly divided into four groups: control group (0.9%NaCl), low-dose imatinib group (50 mg/(kg·d)), medium-dose imatinib group (100 mg/(kg·d)), and high-dose imatinib group (200 mg/(kg·d)). The effect of different concentrations of imatinib administered by continuous gavage on tumor growth was observed for 28 days. HE staining was performed to observe the pathological changes of tumor tissues. The expression of PDGF/PDGFR pathway-related proteins and the phosphorylation levels of AKT and ERK1/2 proteins in tumor tissues were detected by Western blot analysis. Double immunofluorescence staining was used to detect the expression of PDGFB and PDGFRβ proteins in the tumor stroma. Results Imatinib inhibited the growth of A549 non-small cell lung cancer cells in nude mice, suppressed the expression of PDGFB in tumor tissues, and decreased the phosphorylation levels of PDGFRβ, AKT, and ERK1/2. The expression of PDGFB and PDGFRβ in tumor stromal fibroblasts of the administered group was significantly lower than that of the control group. Conclusion Imatinib exhibits a pronounced inhibitory effect on A549 xenografts of nude mice with non-small cell lung cancer, and its antitumor mechanism may involve the downregulation of PDGFB and PDGFRβ expression in tumor stromal fibroblasts.
