Application of cathepsin C inhibitor in treatment of tumor metastasis
A technique for cathepsin and tumor metastasis, applied in the treatment of tumor metastasis, in the field of cathepsin C inhibitors
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Embodiment 1
[0086] CTSC Expression in Breast Cancer Cells with High Lung Metastatic Potential in Example 1
[0087] method:
[0088] We obtained 103 samples of breast cancer in situ and lung metastases, including paired samples of in situ and lung metastases in 7 breast cancer patients. The expression level of CTSC protein in the sample was analyzed by immunofluorescence staining, and the results were as follows: figure 1 A-C shown.
[0089] In order to verify whether CTSC is clinically related to lung metastasis of breast cancer patients, we detected the level of CTSC in serum of breast cancer patients in situ by enzyme-linked immunosorbent assay (ELISA), and then according to the level of CTSC protein in serum of patients The patients were divided into two groups with high CTSC expression and low expression in tumor samples, and the prognosis (transfer-free survival and overall survival) of the two groups were compared by Kaplan-Meier analysis.
[0090] result:
[0091] The analysis...
Embodiment 2
[0096] Example 2 CTSC promotes lung metastasis of breast cancer
[0097] 2.1 Effect of CTSC overexpression on lung metastasis of breast cancer
[0098] method:
[0099] To test whether CTSCs could functionally promote lung metastasis of breast cancer, we overexpressed CTSCs on MDA-MB-231 subline SCP28 with weak lung metastatic potential. Using a model of lung metastasis induced by xenograft tail vein injection, since tumor cells are pre-labeled with luciferase, the growth of tumor cells in lung tissue can be tracked by injecting mice with a luciferase substrate for in vivo imaging.
[0100] Two groups of SCP28 cell lines were set up, namely the blank control SCP28 cell line and the SCP28 cell line of the CTSC overexpression group, and the two groups of cell lines were injected into the mice through the tail vein respectively, and the fluorescence signals of the lung tissues of the two groups of mice were obtained, The number of nodules on the lung surface and the survival ra...
Embodiment 3
[0122] Example 3 AZD7986 (CTSC inhibitor) inhibits lung metastasis of breast cancer
[0123] method:
[0124] Combined with the function of CTSC to promote breast cancer lung metastasis, we further explore the possibility of using CTSC inhibitors to treat breast cancer lung metastasis. AZD7986 is a specific inhibitor of CTSC for the treatment of non-cystic fibrosis bronchiectasis (Non-Cystic Fibrosis Bronchiectasis), and has entered phase II clinical trials (Doyle et al., 2016). We used the orthotopic fat pad injection of 4T1 cells to observe the model of lung metastasis. Seven days after the injection of 4T1 cells, the mice were treated with drugs (AZD7986), and a blank control group was set up. The obtained tumor volume changes with time, the number of lung nodules, the mouse body weight with time, the survival rate of mice, the statistics of neutrophil extracellular traps in lesions, and the schematic diagram are as follows: Figure 5 shown.
[0125] result:
[0126] De...
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