ArticleAmerican journal of cancer research2017
Combination of sorafenib and Valproic acid synergistically induces cell apoptosis and inhibits hepatocellular carcinoma growth via down-regulating Notch3 and pAkt.
Article in American journal of cancer research, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
17 citing papers in PubMed, 24 citations in OpenAlex.
- Mitochondrial gatekeeper in hepatocellular carcinoma: Unraveling the multifaceted roles of VDAC in metabolic reprogramming, apoptosis evasion and therapeutic innovation (Review).Molecular medicine reports · 2026Review
- β-Sitosterol Enhances the Anticancer Efficacy of Oxaliplatin in COLO-205 Cells via Apoptosis and Suppression of VEGF-A, NF-κB-p65, and β-Catenin.International journal of molecular sciences · 2025Article
- Mechanistic Insights about Sorafenib-, Valproic Acid- and Metformin-Induced Cell Death in Hepatocellular Carcinoma.International journal of molecular sciences · 2024Review
- Ramucirumab combination with sorafenib enhances the inhibitory effect of sorafenib on HepG2 cancer cells.Scientific reports · 2022Article
- Isotretinoin and Thalidomide Down-RegulateMolecules (Basel, Switzerland) · 2021Article
- Combined Inhibition of TGF-β1-Induced EMT and PD-L1 Silencing Re-Sensitizes Hepatocellular Carcinoma to Sorafenib Treatment.Journal of clinical medicine · 2021Article
- The Role of Notch3 Signaling in Cancer Stemness and Chemoresistance: Molecular Mechanisms and Targeting Strategies.Frontiers in molecular biosciences · 2021Review
- Curcumin enhances anti‑cancer efficacy of either gemcitabine or docetaxel on pancreatic cancer cells.Oncology reports · 2020Article
- Potential therapies for residual hepatoblastoma following incomplete ablation treatment in a nude mouse subcutaneous xenograft model based on lncRNA and mRNA expression profiles.Oncology reports · 2020Article
- Hepigenetics: A Review of Epigenetic Modulators and Potential Therapies in Hepatocellular Carcinoma.BioMed research international · 2020Review
- Is the era of sorafenib over? A review of the literature.Therapeutic advances in medical oncology · 2020Review
- p21 in Cancer Research.Cancers · 2019Review
- Brivanib in combination with Notch3 silencing shows potent activity in tumour models.British journal of cancer · 2019Article
- Apoptosis of mouse myeloma cells induced by curcumin via the Notch3-p53 signaling axis.Oncology letters · 2019Article
- Sestrin 2 confers primary resistance to sorafenib by simultaneously activating AKT and AMPK in hepatocellular carcinoma.Cancer medicine · 2018Article
- Berberine Inhibits Human Melanoma A375.S2 Cell Migration and Invasion via Affecting the FAK, uPA, and NF-κB Signaling Pathways and Inhibits PLX4032 Resistant A375.S2 Cell Migration In Vitro.Molecules (Basel, Switzerland) · 2018Article
- Fisetin Suppresses Human Osteosarcoma U-2 OS Cell Migration and InvasionIn vivo (Athens, Greece)Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
6 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Sorafenib is currently the only approved first-line targeted drug against advanced hepatocellular carcinoma (HCC). However, unsatisfactory efficacy and resistance of sorafenib raises the urgent need to develop more effective therapeutic strategies for HCC. Here, we evaluated the effects of combination of histone deacetylase inhibitor Valproic acid (VPA) and sorafenib in HCC both in vitro and in vivo. Co-treatment of sorafenib and VPA synergistically inhibited HCC cell viability, induced cell apoptosis, along with the up-regulation of p21, Bax, cleaved caspase9, cleaved caspase3, cleaved PARP and down-regulation of Bcl-xL, suggesting this combination activated intrinsic apoptotic pathway. Our further experiment results showed that sorafenib plus VPA decreased tumor burden more effectively than sorafenib or VPA mono-therapy in nude mice subcutaneous xenograft model. Histological and serological analysis demonstrated well tolerance of this combination in vivo. On a molecular level, our results presented a possible crosstalk between Notch3 and Akt signaling. Sorafenib increased the expression of Notch3 in a dosage dependent manner, along with the phosphorylation of Akt in HCC cells. In comparison, this induction of Notch3 and pAkt could be decreased by VPA, implying that Notch3 and pAkt are of significance in the treatment of HCC, which may account for the synergism of sorafenib and VPA. In conclusion, the combination of sorafenib and VPA offers a potential targeting therapeutic regimen for HCC in the future.
Indexed as
Identifiers
29312803PMC5752690W2973377136What OpenQuestion holds
Registered trials
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.