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. 2023 Jan 6;24(2):1118. doi: 10.3390/ijms24021118

Figure 5.

Figure 5

The suppression of NET formation by NE inhibitors decreased liver metastases. (A) Quantification of HCT116-Luc liver metastatic lesions (photon counts) in KSN/slc nude mice treated with sivelestat (10 mg/kg) or vehicle control. Mean: bars ± SEM. n = 9 mice in each group. * p < 0.05 with Mann–Whitney U test. (B). Representative in vivo bioluminescence images of HCT116-Luc liver metastases in KSN/slc nude mice treated with sivelestat (10 mg/kg) or vehicle control. (C) Representative macroscopic and bioluminescence images of the HCT116-Luc liver metastatic tumors dissected from KSN/slc nude mice treated with sivelestat (10 mg/kg) or vehicle control on day 35. Scale bars, 10 mm. (D). IHC staining for H&E, Cit-H3 and Ki-67 in experimental liver metastasis. Representative images are shown. Scale bars, 500 μm for H&E, 200 μm for Cit-H3 and Ki-67 staining. E and F. Quantification of Cit-H3-positive cells (E) and percentage of Ki-67-positive cells (F) in the IHC staining of xenograft tumors. Mean: bars ± SEM. n = 9 tumors in each group. * p < 0.05 with Student’s t-test. (G) Schematic representation of the possible mechanism by which NETs promote the liver metastasis of CRC cells. NE released during NETosis increases ERK activity, which accelerates the migration of CRC cells. Inhibition of NE suppresses the NETosis and the migration of CRC cells resulting in decreased liver metastases.