ArticleCell communication and signaling : CCS2019
Phloretin attenuates STAT-3 activity and overcomes sorafenib resistance targeting SHP-1-mediated inhibition of STAT3 and Akt/VEGFR2 pathway in hepatocellular carcinoma.
Article in Cell communication and signaling : CCS, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT05546619 (Research on Effectiveness and Safety of the Treatment, Hyperthermic Intraperitoneal Chemotherapy Combined With Tislelizumab and Targeted Therapy, That is Used for High-risk Hepatocellular Carcinoma After R0 Resection), which is not on this map. Cited by 35 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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.
Research on Effectiveness and Safety of the Treatment, Hyperthermic Intraperitoneal Chemotherapy Combined With Tislelizumab and Targeted Therapy, That is Used for High-risk Hepatocellular Carcinoma After R0 Resection
Who cites it
35 citing papers in PubMed, 55 citations in OpenAlex.
- Development of Type II Glucose Transporter Inhibitors: Phloretin as a GLUT-2 Screening Template fromBiomedicines · 2026Article
- Wise as a Serpent and Gentle as a Dove: Pharmacological Targeting of NRF2/KEAP1 Pathway from Treasure Trove of Mother Nature.Drug design, development and therapy · 2026Review
- Rewiring tumor-associated macrophages in hepatocellular carcinoma.Frontiers in immunology · 2026Review
- Harnessing transcriptomics for discovery of natural products to overcome acquired cancer resistance.Archives of pharmacal research · 2026Review
- Current Evidence on the Potential Role of EndothelialReviews in cardiovascular medicine · 2026Review
- Leveraging AI and Natural Compounds: Innovative Approaches in the Diagnosis and Treatment of Hepatocellular Carcinoma.Current pharmaceutical design · 2026Review
- YAP-induced MAML1 cooperates with STAT3 to drive hepatocellular carcinoma progression.Experimental hematology & oncology · 2025Article
- Thoughts on the application of sirolimus.Annals of hematology · 2025Article
- Clusterin-mediated polarization of M2 macrophages: a mechanism of temozolomide resistance in glioblastoma stem cells.Stem cell research & therapy · 2025Article
- Therapeutic Effects of Proanthocyanidins on Diabetic Erectile Dysfunction in Rats.International journal of molecular sciences · 2024Article
- Resveratrol suppresses liver cancer progression by downregulating AKR1C3: targeting HCC with HSA nanomaterial as a carrier to enhance therapeutic efficacy.Apoptosis : an international journal on programmed cell death · 2024Article
- AC099850.3 promotes HBV-HCC cell proliferation and invasion through regulating CD276: a novel strategy for sorafenib and immune checkpoint combination therapy.Journal of translational medicine · 2024Article
- Therapeutic potential of targeting protein tyrosine phosphatases in liver diseases.Acta pharmaceutica Sinica. B · 2024Review
- Three-Dimensional Hepatocyte Spheroids: Model for Assessing Chemotherapy in Hepatocellular Carcinoma.Biomedicines · 2024Article
- Targeting STAT3 and NF-κB Signaling Pathways in Cancer Prevention and Treatment: The Role of Chalcones.Cancers · 2024Review
- Advances in hepatocellular carcinoma drug resistance models.Frontiers in medicine · 2024Review
- CD200-CD200R Pathway: A Regulator of Microglial Polarization in Postoperative Cognitive Dysfunction.Journal of inflammation research · 2024Review
- Development and evaluation of polyacrylamide microspheres loaded with phloretin and tantalum for transcatheter arterial embolization.RSC advances · 2023Article
- Exploring the mechanism of an active ingredient of ginger, dihydrocapsaicin, on triple negative breast cancer based on network pharmacology andOncology letters · 2023Article
- Deciphering STAT3 signaling potential in hepatocellular carcinoma: tumorigenesis, treatment resistance, and pharmacological significance.Cellular & molecular biology letters · 2023Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
5 authors at 4 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundHepatocellular carcinoma (HCC) is the most common primary liver malignancy. Phloretin (PH) possesses anticancer, antitumor, and hepatoprotective effects, however, the effects and potential mechanisms of phloretin remain elusive.
methodsFive HCC cells were tested in vitro for sensitivity to PH, Sorafenib (Sor) or both and the apoptosis, signal transduction and phosphatase activity were analyzed. To validate the role of SHP-1, we used PTP inhibitor III and SHP-1 siRNA. Further, we used purified SHP-1 proteins or HCC cells expressing deletion N-SH2 domain or D61A point mutants to study the PH efficacy on SHP-1. The `in vivo studies were conducted using HepG2 and SK-Hep1 and Sor resistant HepG2
resultsPH inhibited cell growth and induced apoptosis in all HCC cells by upregulating SHP-1 expression and downregulating STAT3 expression and further inhibited pAKT/pERK signaling. PH activated SHP-1 by disruption of autoinhibition of SHP-1, leading to reduced p-STAT3
conclusionOur data suggest that PH inhibits STAT3 activity in Sor-sensitive and -resistant HCCs via SHP-1-mediated inhibition of STAT3 and AKT/mTOR/JAK2/VEGFR2 pathway. Our results clearly indicate that PH may be a potent reagent for hepatocellular carcinoma and a noveltargeted therapy for further clinical investigations.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.