The combination of ATN-161 and 5-FU results in a notable reduction in tumor cell proliferation compared to both control and monotherapy (p<0.01). Furthermore, the combined treatment leads to a significant increase in apoptotic (TUNEL-positive) tumor cells (p<0.03), whereas monotherapy does not increase the number of TUNEL-positive tumor cells. Following a 48-hour incubation period, ATN-161 treatment leads to a significant decrease in endothelial cell (EC) count (21% reduction) compared to control (p<0.03) [1]. ATN-161 inhibits VEGF-induced migration and capillary tube formation in hCECs, while showing no effect on proliferation. It reduces the number of cells migrating in response to VEGF in a dose-dependent manner, starting at 100 nM (P<0.001 vs. VEGF group)[2].
体内研究
Preliminary experiments conducted with α5β1-negative human colon cancer xenografts (HT29) demonstrate that ATN-161 treatment significantly decreases both tumor weight and vessel density [1].
Administration of ATN-161 following laser photocoagulation effectively suppresses choroidal neovascularization (CNV) leakage and neovascularization to a degree comparable to that of AF564 [2].
体外研究
The combination of ATN-161 and 5-FU results in a notable reduction in tumor cell proliferation compared to both control and monotherapy (p<0.01). Furthermore, the combined treatment leads to a significant increase in apoptotic (TUNEL-positive) tumor cells (p<0.03), whereas monotherapy does not increase the number of TUNEL-positive tumor cells. Following a 48-hour incubation period, ATN-161 treatment leads to a significant decrease in endothelial cell (EC) count (21% reduction) compared to control (p<0.03) [1].
ATN-161 inhibits VEGF-induced migration and capillary tube formation in hCECs, while showing no effect on proliferation. It reduces the number of cells migrating in response to VEGF in a dose-dependent manner, starting at 100 nM (P<0.001 vs. VEGF group)[2].
ATN-161 细胞实验
Cell Line
Concentration
Treated Time
Description
References
Huh7 cells
10 µMol/ml
24 hours
Inhibited OCT4 mRNA expression
J Transl Med. 2022 Dec 3;20(1):555.
VeroE6 cells
1 µM to 10 µM
1 hour
To assess the ability of ATN-161 to inhibit SARS-CoV-2 infection. Results showed that ATN-161 increased cell viability at concentrations as low as 1 μM and reduced cytopathic effects at 10 μM.
JACC Basic Transl Sci. 2021 Jan;6(1):1-8.
DU145 prostate cancer cells
1 μg/ml
24 hours
To evaluate the inhibitory effect of PHSCN peptide on the invasive ability of DU145 cells. Results showed that PHSCN peptide significantly reduced the invasive ability of DU145 cells, with a six-fold decrease compared to untreated cells.
Neoplasia. 2002 Sep-Oct;4(5):373-9.
HCCLM3 cells
10 µMol/ml
24 hours
Inhibited NANOG and OCT4 mRNA expression, reduced YAP activation
J Transl Med. 2022 Dec 3;20(1):555.
Human aortic endothelial cells (HAECs)
50 µM
30 minutes
To evaluate the effect of ATN-161 on shear stress-induced endothelial cell activation. Results showed that ATN-161 did not affect shear stress-induced activation of FAK, PAK2, and NF-κB.
Am J Pathol. 2015 Sep;185(9):2575-89.
HEK293T-ACE2 cells
0.1 mM
6 hours
Investigate the effect of ATN-161 on rVSV-S infection, results showed that ATN-161 exhibited no inhibition effect on rVSV-S infection
Proc Natl Acad Sci U S A. 2023 Dec 12;120(50):e2311913120.
CD4/H11001CD45RBhigh T-cell transfer colitis model
Intraperitoneal injection
1 mg/kg
Three times a week for six weeks
ATN-161 significantly reduced histopathological scores and angiogenic index in CD4/H11001CD45RBhigh colitis, indicating its therapeutic effect by inhibiting angiogenesis during experimental colitis.
Am J Pathol. 2006 Dec;169(6):2014-30
Mice
IL10-deficient mice and DSS-induced colitis model
Intraperitoneal injection
1 mg/kg
Every other day for 6 weeks
To evaluate the therapeutic effect of ATN-161 on experimental colitis. Results showed that ATN-161 significantly reduced the Disease Activity Index (DAI), histological colitis score, and mean vascular density (MVD), and decreased the production of inflammatory cytokines.
Gut. 2007 Jun;56(6):855-62
K18-hACE2 transgenic mice
SARS-CoV-2 infection model
Intravenous injection
1 mg/kg
Single or repeated doses within 48 hours post-infection
Reduced lung viral load, viral immunofluorescence, and improved lung histology
Life Sci. 2021 Nov 1;284:119881
Mice
Ischemic stroke model
Intraperitoneal injection
1 mg/kg
Immediately after reperfusion, on post-stroke day (PSD)1 and PSD2
To evaluate the therapeutic effects of ATN-161 on ischemic stroke, results showed ATN-161 significantly reduced infarct volume, edema, and functional deficits, while also reducing BBB permeability and inflammatory responses
To test whether combination treatment of ATN-161 with hNSC transplantation further benefits stroke outcome. Results showed that ATN-161 combined with hNSC transplantation reduced infarct size and attenuated the induction of proinflammatory factors and matrix metalloproteases.
Exp Neurol. 2022 Jan;347:113913
ApoE knockout mice
Atherosclerosis model
Intraperitoneal injection
5 mg/kg
Three times per week for 7 days
To evaluate the effect of ATN-161 on atherosclerotic plaque formation. Results showed that ATN-161 did not affect plaque formation or inflammatory responses.
Am J Pathol. 2015 Sep;185(9):2575-89.
ApoE-deficient mice
High-fat Western Diet-induced atherosclerosis model
Intraperitoneal injection
5 mg/kg
Three times a week for 8 weeks
Evaluate the effect of ATN-161 on atherosclerotic plaque development
Three times per week, continued until the end of the experiment
To evaluate the inhibitory effect of PHSCN peptide on DU145 tumor recurrence and metastasis. Results showed that PHSCN peptide significantly inhibited tumor recurrence and metastasis, with all treated mice remaining recurrence- and metastasis-free for 30 weeks post-surgery.
搜索
