التفاصيل البيبلوغرافية
| العنوان: |
Effects of vesicular stomatitis virus on anti-tumour immunity, growth of xenografts, and lung metastasis in mouse mammary carcinoma 4T1 cells tumor-bearing mice. (English) |
| المؤلفون: |
LI Yuqian, XU Qingsheng, WEI Hong, WANG Hao, WANG Shuoshi, JIANG Lina, YUAN Xinyi |
| المصدر: |
Chinese Journal of Cancer Biotherapy; May2024, Vol. 31 Issue 5, p452-461, 10p |
| مصطلحات موضوعية: |
STOMATITIS, BIOLOGICAL models, CELL migration, FLOW cytometry, CANCER, BREAST tumors, POLYMERASE chain reaction, ENZYME-linked immunosorbent assay, XENOGRAFTS, HUMAN growth, CANCER patients, TUMOR markers, METASTASIS, CELL lines, MICE, IMMUNOHISTOCHEMISTRY, MESSENGER RNA, SERUM, GENE expression, LUNG tumors, ANIMAL experimentation, MICROBIOLOGICAL assay, MATRIX metalloproteinases, VIRUS diseases, STAINS & staining (Microscopy), IMMUNITY, INTERLEUKINS, TUMOR necrosis factors |
| مستخلص: |
Objective: To investigate the effects of wild-type vesicular stomatitis virus strain (VSV-IN) on immunomodulation and tumour metastasis in mouse triple negative breast cancer (TNBC) 4T1 cell transplantation model mice. Methods: After VSV-IN infected 4T1 cells with MOI=1, MOI=10 and MOI=100 for 12, 24 and 48 h, 4T1 cell mortality was detected by CCK-8 method, migration ability by scratch healing assay, and the expressions of E-cadherin, MMP-2 and MMP-9 mRNA by qPCR. The fat pads of female BALB/c mice were inoculated with 0.1 mL of 4T1 cells with a cell density of 1x106 cells/mL to construct a 4T1 cell-loaded mouse model. When the tumour volume reached 200 mm³, the mice were injected intratumorally with PBS, taxol (TAX) (15 mg/kg), and VSV (1x106 pfu) once a week, respectively. After 4 administrations, mice were executed, stripped of intact grafted tumour tissues, and tumour volume and mass were measured. Histopathological sections of the lungs were stained with H-E, and tumour metastatic nodules of the lungs were observed. The proportion of T-cell subpopulations in the spleen was detected by flow cytometry. The levels of serum IL-6 and TNF-α were detected by ELISA. The expression levels of migration-related proteins in mammary gland tumours were analysed by using the online analysis of GEPIA. The expressions of MMP-2, MMP-9 and E-cadherin in mouse tumours were detected by immunohistochemistry, and the affinity of G and M proteins of VSV-IN and ERK2 and E-cadherin was predicted by protein-protein docking technology. Results: The mortality rate of 4T1 cells after 48 hours of VSV treatment at MOI=10 and 100 were significantly higher than that of the control group (P<0.01). Compared with that of the control group, the cell migration rate of the VSV-IN group (MOI=10) was significantly lower (P<0.01), and the relative expression of MMP-9 mRNA was significantly lower (P<0.05). Compared with those in the mice of the control group, transplanted tumours in the mice of the VSV-IN group grew more slowly, and their endpoint volume was significantly reduced (P<0.05). The number of lung metastatic nodules in the mice of the VSV group was significantly less than that of the control group ([12.86±1.86] vs [24±3.67], P<0.01). The proportions of splenic CD4+ T and CD8+ T cells in the VSV group were significantly higher (both P<0.05). The serum TNF-α and IL-6 levels were significantly higher (both P< 0.01). GEPIA tool analysis revealed that the expression levels of E-cadherin and MMP-9 were higher in breast cancer tissues than in paracancerous tissues (P<0.05). The expression of MMP-9 in the tumour cells of the mice in the VSV-IN group was significantly lower than that in the control group (P<0.05). The binding free energies of G and M proteins of VSV-IN to ERK2 were -11.7 kcal/mol and -6.4 kcal/mol, respectively. Conclusion: Wild-type VSV-IN inhibits the growth and metastasis of transplanted tumours in 4T1 tumor-bearing mice, which may be related to its promotion of anti-tumour immunity and modulation of the expression of migration-related proteins. [ABSTRACT FROM AUTHOR] |
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| قاعدة البيانات: |
Complementary Index |
