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Inhibitory Effects of LR-MSCs on the LUAD Growth by Reducing Angiogenesis
Vol 37, Issue 10, 2023
Abstract
Background: Lung adenocarcinoma (LUAD) is the most common type of lung cancer. At present, stem cell therapy has gradually attracted attention in LUAD treatment. Therefore, this study was designed to explore the effects and mechanisms of lung-resident mesenchymal stem cells (LR-MSCs) on LUAD. Methods: Xenograft tumor models of LUAD mice were established and randomly divided into four groups, namely human umbilical cord mesenchymal stem cells (hUCMSCs), LR-MSCs and gemcitabine (GEM) treatment groups as well as the normal saline (NS) group. The tumor growth volume was recorded every 3 days, and after 21 days, the nude mice were sacrificed. Subsequently, pathological changes of the tumor, lung, and liver tissues were observed by hematoxylin and eosin (H&E) staining; protein expressions of vascular endothelial growth factor (VEGF), B-cell lymphoma-2 (BCL-2), and matrix metalloproteinase-9 (MMP-9) were examined by immunohistochemistry. Results: Xenograft tumor models of LUAD mice were successfully established. Compare with the NS group, the treatment groups had smaller volume and size of xenograft tumors. Besides, the results of H&E staining showed slighter pathological changes of tumor tissues in the treatment groups than those in the NS group. Therefore, MSCs may inhibit the growth of subcutaneous xenograft tumors. Furthermore, the protein expression levels of VEGF and BCL-2 in tumor tissues of each treatment group were significantly lower than those in the NS group. Notably, the MMP-9 protein of the LR-MSCs and GEM treatment groups were significantly lower than that of the NS group and hUCMSCs group. The inhibition of tumor growth by MSCs may be related to its functions that controlled angiogenesis in tumors and promoted rapid apoptosis of tumor cells. Additionally, no metastases and liver injury were observed in the liver tissues of nude mice. Conclusion: LR-MSCs can inhibit the growth of subcutaneous xenograft tumors in LUAD nude mice by down-regulating the expressions of VEGF and BCL-2 proteins, Moreover, the effect of LR-MSCs is comparable to that of hUCMSCs.
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Medical Genetics, University of Torino Medical School, Italy
Department of Biomedical, Surgical and Dental Sciences, University of Milan, Italy