Papers
Chinese title: thalidomide VEGFA expression and PD-1/PD-L1 mediated by lncRNA FGD5-AS1/miR-454-3p/ZEB1 axis Checkpoints inhibit NSCLC angiogenesis and immune escape
English title: Thalidomide suppresses angiogenesis and immune expression evasion via lncRNA1 F and 5-AS-mediated/ZER-454-3 PD-1/PD-L1 checkpoint in NSCLC
Magazine name: Chemico-biological interactions
Impact factor: 5.192
on September 11, 2021 p5p
Chinese summary
About 80-85% of lung cancer patientsDetermining the molecular mechanism of anti-tumor drugs is essential to improve the therapeutic effect. Here, this article aims to study the role of thalidomide in the tumorigenicity of NSCLC.
This study established an A549 nude mouse xenograft model to observe the therapeutic effect of thalidomide. To evaluate the expression of FGD5-AS1 in cancer tissues and adjacent tissues of NSCLC patients and NSCLC cell lines, perform CCK-8 test to evaluate cell viability; use transwell test to check invasion ability, use tube test to determine cell angiogenesis; flow cytometry Cytometry verifies the activity of CD8+ T cells . Use luciferase reporter gene, RIP and ChIP detection to analyze the FGD5-AS1/miR-454-3p/ZEB1 regulatory network.
Results showed that thalidomide reduced tumor growth and T cell ratio in the mouse model, and increased CD8. The increased expression of FGD5-AS1 is positively correlated with the poor survival of NSCLC patients. Knockout of FGD5-AS1 can significantly inhibit the proliferation, invasion and angiogenesis of cancer cells and the apoptosis of CD8+ T cells.
Thalidomide targets FGD5-AS1 to exert anti-tumor activity in NSCLC.
FGD5-AS1 as the sponge of miR-454-3p up-regulates ZEB1, thereby increasing the expression of programmed death ligand 1 (PD-L1) and vascular endothelial growth factor_VEGFspan8 ; Simultaneous overexpression of FGD5-AS1 and silencing miR-454-3p can reverse the anti-tumor effect of thalidomide-mediated NSCLC.
The results showed that thalidomide expressed through FGD5-AS1/miR-454-3p/E-box zinc finger protein mediated by FGD5-AS1/miR-454-3p/E box zinc finger protein Regulation of programmed death ligand 1 (PD-1)/PD-L1 checkpoint inhibits NSCLC angiogenesis and immune escape.
original link: https://pubmed.ncbi.nlm.nih.gov/34520751
Comment:
Salle Thalidomide (Thalidomide) is a glutamic acid derivative.Mechanism of action has: ①Sedation of pain. ②Immune regulation and anti-inflammatory effects of . ③Inhibition of angiogenesis and anti-tumor effect : Some cytokines, such as vascular endothelial growth factor and fibroblasts, are stimulators of angiogenesis, and they bind to specific receptors to stimulate signal transduction and cause endothelial cells proliferation, thalidomide can reduce their secretion, thereby inhibiting blood vessels; tumor metastasis and cell malignancy are related to the adhesion of tumor cells and vascular endothelial cells, and angiogenesis. Thalidomide not only inhibits angiogenesis, And it can reduce the synthesis of integrin subunits, which is also one of its anti-tumor mechanisms. In addition, the COX-2 pathway is used instead of the pathway to inhibit angiogenesis to reduce the intratumoral microvessel density, thereby preventing tumor proliferation.
Multiple clinical studies have shown thalidomide in breast cancer, mantle cell lymphoma and Hodgkin lymphoma and other solid and hematological tumors It has anti-tumor activity, especially the first-line treatment of multiple myeloma (MM). This study preliminarily shows that thalidomide can play a certain anti-tumor effect in lung cancer. has the hope of becoming an effective drug for the treatment of lung cancer in the future.
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