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Home > Archive>Volume 31, Issue 7, 2023 >871-879. DOI:10. 3969 / j.issn.1005-4847. 2023. 07. 005
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Effect of Astragalus polysaccharides on HIF-1 and S100A8/ A9 protein expression in the pre-metastatic niche of lung tumors and lung metastasis
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1. School of Basic Medicine, Gansu University of Chinese Medicine, Lanzhou 730000, China. 2. Basic Discipline of Integrative Traditional Chinese and Western Medicine, Gansu University of Chinese Medicine, Lanzhou 730000. 3. Gansu University Key Laboratory for Molecular Medicine & Chinese Medicine Prevention and Treatment of Major Diseases, Gansu University of Chinese Medicine, Lanzhou 730000. 4. Key Laboratory of Chronic Diseases for Prevention and Treatment of Traditional Chinese Medicine, Lanzhou 730000. 5. Affiliated Hospital of Gansu University of Chinese Medicine, Lanzhou 730000

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    Abstract:

    Objective To observe the effects of different concentrations of Astragalus polysaccharides (APS) on hypoxia-inducible factor (HIF)-1 and S100A8/ A9 protein expression in the lung pre-metastatic niche(PMN), and to investigate the targets of APS in lung PMNs and its molecular mechanisms in relation to lung tumor metastasis. Methods Ninety specific-pathogen-free C57BL/6J mice were used, of which 15 were set as the blank control group. A PMN model was constructed in the remaining 75 mice by tail vein injection of 1 × 106 luciferase-labeled Lewis lung cancer cells. These 75 mice were divided randomly into five groups (n = 15 per group): model, low-dose (APS 50 mg/ kg), medium-dose (APS 100 mg/ kg), high-dose (APS 200 mg/ kg), and fingolimod (FTY720, injected intraperitoneally 1 mg/ kg) groups. APS was administered by gavage at the respective prescribed dose once a day on the day after inoculation of tumor cells and FTY720 was administered once every 2 days. The effects of different concentrations of APS on HIF-1 and S100A8/ A9 proteins in the PMN was observed and lung metastasis was assessed by hematoxylin/ eosin (HE) staining. On day 14, five mice from each group were randomly selected and lung tissues were removed and multifunctional proteoglycans, fibronectin, and lysyl oxidase were detected by Western Blot and Real-time qvantitative PCR (RT-qPCR), and histopathological changes in the lung were observed by HE staining. Protein and gene expression levels of HIF-1 and S100A8/ A9 in lung tissues taken at 28 days were also detected by Western Blot and RT-qPCR. Mice were fasted but had access to water for 12 h before sampling. Results HE staining revealed alveolar wall thickening and granulocyte infiltration with a few tumor metastases in lung tissues in the model group. Tumor metastatic foci were significantly reduced and the lung tissues tended to be normal in the high-dose and FTY720 groups compared with the model group. HIF-1, S100A8, and S100A9 protein and gene expression levels were significantly higher in the lungs of mice in the model groups compared with the blank group (P< 0. 05), according to Western Blot and RT-qPCR. In contrast, the above protein and gene expression levels were decreased in the FTY720 group and all APS groups compared with the model group (P< 0. 05). Conclusions APS can reduce lung metastasis of tumor cells by regulating the expression levels of HIF-1, S100A8 and S100A9 in the PMN of lung tumors.

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History
  • Received:January 13,2023
  • Online: October 17,2023
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