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Archive > Volume 30 Issue 7 > 2023,30(7):568-576. DOI:10.3872/j.issn.1007-385X.2023.07.004 Prev Next
Basic Research
Possible mechanism of 191 measles attenuated live vaccine strains inhibiting the proliferation of triple negative breast cancer MDA-MB-231 cells based on proteomics technology
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Abstract:
Objective: To investigate the effect and mechanism of live attenuated measles vaccine strain 191 (MV-Hu191) on triple negative breast cancer MDA-MB-231 and 4T1 cells in vitro and in vivo based on proteomics. Methods: CCK-8 method was used to analyze the effect of MV-Hu191 on the proliferation of MDA-MB-231 and 4T1 cells. Liquid chromatography-mass spectrometry was used to analyze the effect of MV-Hu191 treatment on protein spectrum in MDA-MB-231 cells. Multiple databases were used to screen typical differentially expressed proteins, followed with GO, KEGG, subcellular localization and functional annotation. Intratumoral injection of 1×106 TCID50 MV-Hu191 was used to intervene the growth of 4T1 cell transplanted tumor in mice. Flow cytometry was applied to detect T cell subpopulations in splenic tissue, and ELISA was used for the detection of serum levels of TNF-α and IL-6. Results: In vitro experiments showed that MV-Hu191 could significantly inhibit the proliferation of MDA-MB-231 and 4T1 cells (P<0.01). Proteomic analysis showed that 38 proteins were significantly upregulated while 12 proteins were downregulated in MDA-MB-231 cells after MV-Hu191 treatment. The differentially expressed proteins were mainly involved in the biological processes of cell adhesion, signaling receptor activation, cell metabolism, and stress responses. The subcellular localization of 22 differentially expressed proteins was located outside the cell. The KEGG functional classification showed that the most differentially expressed proteins were related to immunomodulatory functions and they were all upregulated, including C4A, C8B, SERPINF2, A2M, SERPINC1, CTSB, SERPING1, and C5; PPI prediction found immune-related differential proteins were associated with CD4, CD8, TNF-ɑ and IL-6. In vivo experiments showed that the number of CD4+ T cells in spleen tissues of mice in the MV-Hu191 intervention group was higher than that in the control group, but the difference was not significant (P>0.05). The ratio of CD4+/CD8+ T cells and the serum levels of TNF-ɑ and IL-6 in the MV-Hu191 intervention group were significantly higher than those in the control group (P<0.05, P<0.01). Conclusion: MV-Hu191 significantly inhibits the proliferation of MDA-MB-231 and 4T1 cells and antagonizes the tumorigenicity in mice bearing 4T1 cell xenograft. The mechanism may be that MV-Hu191 achieve its anti-tumor effect by activating immune effector molecules.
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