AI Article Synopsis
- Oxaliplatin-resistant LoVo colon cancer cells show increased c-MET and VEGFR-1 expression compared to chemosensitive cells, but surprisingly have reduced VEGF levels.
- These resistant cells also activate additional signaling pathways related to chemoresistance, including Akt and β-catenin-TCF4, while the phosphorylation of c-MET is decreased when VEGF is introduced into their environment.
- VEGF inhibits c-MET phosphorylation through VEGFR-1, and when VEGFR-1 is silenced, the phosphorylation of c-MET is restored, indicating a complex interaction that may impact the effectiveness of anti-VEGF therapies in tumors expressing both receptors.
Article Abstract
Oxaliplatin-resistant LoVo colon cancer cells overexpressing c-MET and VEGFR-1 were selected to study several signaling pathways involved in chemoresistance, as well as the effect of increasing amounts of VEGF in the regulation of c-MET. In comparison with chemosensitive LoVo colon cancer cells, oxaliplatin-resistant cells (LoVoR) overexpress and phosphorylate c-MET, upregulate the expression of transmembrane and soluble VEGFR-1 and, unexpectedly, downregulate VEGF. In addition, LoVoR cells activate other transduction pathways involved in chemoresistance such as Akt, β-catenin-TCF4 and E-cadherin. While c-MET is phosphorylated in LoVoR cells expressing low levels of VEGF, c-MET phosphorylation decreases when recombinant VEGF is added into the culture medium. Inhibition of c-MET by VEGF is mediated by VEGFR-1, since phosphorylation of c-MET in the presence of VEGF is restored after silencing VEGFR-1. Dephosphorylation of c-MET by VEGF suggests that tumors coexpressing VEGFR-1 and c-MET may activate c-MET as a result of anti-VEGF therapy.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1002/mc.22289 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
New Hydrazone Derivatives Based on Pyrazolopyridothiazine Core as Cytotoxic Agents to Colon Cancers: Design, Synthesis, Biological Evaluation, and Molecular Modeling.
ChemMedChem
January 2025
Danylo Halytsky Lviv National Medical University, Pharmaceutical, Organic and Bioorganic Chemistry, UKRAINE.
In this research, a series of novel hydrazone derivatives based on pyrazolopyridothiazinylacetohydrazide were designed, synthesized, and evaluated for their in vitro cytotoxic potency on several human colon cancer cells (HTC116, HT-29, and LoVo). After MTT and SRB assays four of the most active derivatives: hydrazide GH and hydrazones GH7, GH8, and GH11, were chosen for further investigation. Hydrazone GH11 had the highest cytotoxic activity (IC50 values of c.
View Article and Find Full Text PDFmiR-105-5p/PTEN Axis Modulates the Immune Response and Epithelial-Mesenchymal Transition of Colon Cancer via NF-κB Activation.
J Biochem Mol Toxicol
January 2025
Department of Anorectal, Affiliated Hospital of Jiaxing University, The Second Hospital of Jiaxing, Jiaxing City, Zhejiang Province, China.
The underlying regulating mechanisms of miR-105-5p/PTEN in colon cancer (CC) progression are still unknown. MiR-105-5p and PTEN expressions were determined using RT-PCR. PTEN protein levels were examined by western blot.
View Article and Find Full Text PDFCigarette smoke-induced attenuation of the prostaglandin transporter SLCO2A1 expression through aryl hydrocarbon receptor.
Prostaglandins Other Lipid Mediat
November 2024
Laboratory of Membrane Transport and Biopharmaceutics, Faculty of Pharmacy, Takasaki University of Health and Welfare, Takasaki, 370-0033, Japan. Electronic address:
SLCO2A1 is a prostaglandin transporter and contributes to regulating local concentration of an inflammatory mediator, PGE. Since we previously found that cigarette smoke extracts (CSE) reduced Slco2a1 mRNA expression in rat alveolar epithelial cells, the current study aimed to investigate the effect of CSE on human SLCO2A1 mRNA expression across cell lines from organs that are susceptible to tobacco smoking-induced inflammation. 5'-Flanking regions of SLCO2A1 up to 3673 bp upstream of the transcription start site (+1) was sub-cloned into a luciferase (LUC) expression vector, and promoter activity was evaluated by a reporter assay.
View Article and Find Full Text PDFOxaliplatin and 5-fluorouracil promote epithelial-mesenchymal transition via activation of KRAS/ERK/NF-κB pathway in KRAS-mutated colon cancer cells.
Mol Cell Biochem
November 2024
Kindai University Faculty of Pharmacy, Kowakae, Higashiosaka, Osaka, 577-8502, Japan.
Oxaliplatin (L-OHP) and 5-fluorouracil (5-FU) are used to treat colon cancer; however, resistance contributes to poor prognosis. Epithelial-mesenchymal transition (EMT) has been induced in tumor tissues after administration of anticancer drugs and may be involved in drug resistance. We investigated the mechanism of EMT induction in colon cancer cells treated with 5-FU and L-OHP.
View Article and Find Full Text PDFBroussoflavonol F exhibited anti-proliferative and anti-angiogenesis effects in colon cancer via modulation of the HER2-RAS-MEK-ERK pathway.
Phytomedicine
December 2024
Institute of Chinese Medicine and State Key Laboratory of Research on Bioactivities and Clinical Applications of Medicinal Plants, The Chinese University of Hong Kong, Shatin, New Territories, Hong Kong SAR, China; Department of Pharmacology and Pharmacy, LKS Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong SAR, China; School of Chinese Medicine, LKS Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong SAR, China. Electronic address:
Background: A prenylated flavonoid, broussoflavonol F (BFF), was isolated from Macaranga genus with cytotoxicities against various cancer cells, though its underlying mechanisms have not been fully elucidated.
Hypothesis: This study aimed to investigate the anti-tumor and anti-angiogenesis activities of BFF and its underlying mechanisms in colon cancer.
Method: In the in vitro study, the cytotoxic effects of BFF in human colon cancer HCT-116 and LoVo cells were examined using MTT assay, BrdU assay and colony formation assay.
Want AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!