ArticleOncotarget2017
Autocrine VEGF signaling promotes cell proliferation through a PLC-dependent pathway and modulates Apatinib treatment efficacy in gastric cancer.
Article in Oncotarget, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT04182698 (Phase I / II Clinical Study on the Safety and Preliminary Efficacy of Anlotinib Hydrochloride Combined With Platinum-containing Simultaneous Radiotherapy in the Treatment of Locally Advanced Non-small Cell Lung Cancer), which is not on this map. Cited by 39 papers.
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The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Phase I / II Clinical Study on the Safety and Preliminary Efficacy of Anlotinib Hydrochloride Combined With Platinum-containing Simultaneous Radiotherapy in the Treatment of Locally Advanced Non-small Cell Lung Cancer
Who cites it
39 citing papers in PubMed, 69 citations in OpenAlex.
- Apatinib Mesylate in the treatment of advanced progressed lung adenocarcinoma patients with EGFR-TKI resistance -A Multicenter Randomized Trial.Scientific reports · 2019Trial
- MicroRNA-VEGF axis in gastric cancer: a novel therapeutic frontier.Discover oncology · 2026Review
- A dimer peptide ligand of vascular endothelial growth factor slows the progression of human gastric tumors in mouse xenografts.PloS one · 2026Article
- Precision Antibody Therapy in Gastric and Gastroesophageal Cancer: Targeting FGFR2b, CLDN18.2, and VEGFR2.Cells · 2025Review
- Advances in research on the effects of medicinal and edible substances on lung cancer: an updated review.Frontiers in pharmacology · 2025Review
- Pembrolizumab in combination with trastuzumab for treatment of HER2-positive advanced gastric or gastro-esophageal junction cancer.Annals of medicine and surgery (2012) · 2024Review
- Review
- The multiple combination of Paclitaxel, Ramucirumab and Elacridar reverses the paclitaxel-mediated resistance in gastric cancer cell lines.Frontiers in oncology · 2023Article
- Exosomal circ_0001190 Regulates the Progression of Gastric Cancer via miR-586/SOSTDC1 Axis.Biochemical genetics · 2022Article
- Targeting VEGF with bevacizumab inhibits malignant effusion formation of primary human herpesvirus 8-unrelated effusion large B-cell lymphoma in vivo.Journal of cellular and molecular medicine · 2022Article
- Cholenic acid derivative UniPR1331 impairs tumor angiogenesis via blockade of VEGF/VEGFR2 in addition to Eph/ephrin.Cancer gene therapy · 2022Article
- Molecular pathogenesis and emerging targets of gastric adenocarcinoma.Journal of surgical oncology · 2022Review
- Inhibition of the VEGF signaling pathway attenuates tumor‑associated macrophage activity in liver cancer.Oncology reports · 2022Article
- Nonsynonymous C1653T Mutation of Hepatitis B Virus X Gene Enhances Malignancy of Hepatocellular Carcinoma Cells.Journal of hepatocellular carcinoma · 2022Article
- Early increase of plasma soluble VEGFR-2 is associated with clinical benefit from second-line treatment of paclitaxel and ramucirumab in advanced gastric cancer.American journal of cancer research · 2022Article
- The Role of Lipid Metabolism in Gastric Cancer.Frontiers in oncology · 2022Review
- Single-cell landscape reveals active cell subtypes and their interaction in the tumor microenvironment of gastric cancer.Theranostics · 2022Article
- Variations in Circulating Levels of Angiopoietin-2 Over Time Are Predictive of Ramucirumab-Paclitaxel Therapy Outcome in Advanced Gastric Cancer: Results of Prospective Study.Frontiers in oncology · 2022Article
- LncRNA ZNFTR functions as an inhibitor in pancreatic cancer by modulating ATF3/ZNF24/VEGFA pathway.Cell death & disease · 2021Article
- Apatinib inhibits gastric carcinoma development by regulating the expression levels of IL-17 via the Bax/Bcl-2 signaling pathway.Experimental and therapeutic medicine · 2021Article
Corrections and comments
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Authors and funding
10 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundTumor cells produce vascular endothelial growth factor (VEGF) which interact with the membrane or cytoplasmic VEGF receptors (VEGFRs) to promote cell growth in an angiogenesis-independent fashion. Apatinib, a highly selective VEGFR2 inhibitor, is the only effective drug for patients with terminal gastric cancer (GC) who have no other chemotherapeutic options. However, its treatment efficacy is still controversy and the mechanism behind remains undetermined. In this study, we aimed to investigate the role of autocrine VEGF signaling in the growth of gastric cancer cells and the efficacy of Apatinib treatment.
methodsThe expression of phosphor VEGFR2 in gastric cancer cell lines was determined by real-time PCR, immunofluorescence, and Western blot. The gastric cancer cells were administrated with or without recombination human VEGF (rhVEGF), VEGFR2 neutralizing antibody, U73122, SU1498, and Apatinib. The nude mice were used for xenograft tumor model.
resultswe found that autocrine VEGF induced high VEGFR2-expression, promoted phosphorylation of VEGFR2, and further enhanced internalization of pVEGFR2 in gastric cancer cells. The autocrine VEGF was self-sustained through increasing VEGF mRNA and protein expression. It exerted pro-proliferative effect through a PLC-ERK1/2 dependent pathway. Furthermore, we demonstrated that in VEGFR2 overexpressing gastric cancer cells, Apatinib inhibited cell proliferation in vitro and delayed xenograft tumor growth in vivo. However, these effects were not observed in VEGFR2 low expressing gastric cancer cells.
conclusionThese results suggested that autocrine VEGF signaling promotes gastric cancer cell proliferation and enhances Apatinib treatment outcome in VEGFR2 overexpression gastric cancer cells both in vitro and in vivo. This study would enable better stratification of gastric cancer patients for clinical treatment decision.
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