ArticleJournal of experimental & clinical cancer research : CR2016
Enhancement of anti-tumor effects of 5-fluorouracil on hepatocellular carcinoma by low-intensity ultrasound.
Article in Journal of experimental & clinical cancer research : CR, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.
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Who cites it
30 citing papers in PubMed, 58 citations in OpenAlex.
- Biomimetic M2 exosome-based dual-drug nanoplatform for combined immunomodulation and bone protection in rheumatoid arthritis.Bioactive materials · 2026Article
- Glutathione metabolism-associated resistance to cisplatin and 5-FU in esophageal cancer: a paired transcriptomic study.BMC gastroenterology · 2026Article
- Bacillus velezensis MZ09 alleviates DSS-induced colitis in piglets by remodeling the intestinal microbiota activating the SCFAs-GPR43-STAT3 pathway and suppressing NLRP3 inflammasome-mediated pyroptosis.Journal of animal science and biotechnology · 2025Article
- Comparative analysis of ALA mediated sonodynamic therapy considering tumor size, light combination and ultrasound delivery in murine cutaneous melanoma.Scientific reports · 2025Article
- The spatiotemporal heterogeneity of reactive oxygen species in the malignant transformation of viral hepatitis to hepatocellular carcinoma: a new insight.Cellular & molecular biology letters · 2025Review
- Antitumor Effects of Pegylated Zinc Protoporphyrin-Mediated Sonodynamic Therapy in Ovarian Cancer.Pharmaceutics · 2023Article
- Heterogeneity characterization of hepatocellular carcinoma based on the sensitivity to 5-fluorouracil and development of a prognostic regression model.Frontiers in pharmacology · 2023Article
- Mifepristone inhibits hepatoma growth by enhancing the GR-HSP60-survivin interaction to facilitate survivin degradation.Journal of Cancer · 2023Article
- Biomimetic cytomembrane-coated ZIF-8-loaded DMDD nanoparticle and sonodynamic co-therapy for cancer.Annals of translational medicine · 2022Article
- Low-frequency ultrasound irradiation increases paclitaxel-induced sarcoma cells apoptosis and facilitates the transmembrane delivery of drugs.Frontiers in pharmacology · 2022Article
- Low-Intensity Focused Ultrasound Targeted Microbubble Destruction Enhanced Paclitaxel Sensitivity by Decreasing Autophagy in Paclitaxel-Resistant Ovarian Cancer.Frontiers in oncology · 2022Article
- APR-246 induces apoptosis and enhances chemo-sensitivity via activation of ROS and TAp73-Noxa signal in oesophageal squamous cell cancer with TP53 missense mutation.British journal of cancer · 2021Article
- Bitter melon derived extracellular vesicles enhance the therapeutic effects and reduce the drug resistance of 5-fluorouracil on oral squamous cell carcinoma.Journal of nanobiotechnology · 2021Article
- Bioactivity Studies of Hesperidin and XAV939.ACS omega · 2021Article
- Ultrasound cavitation enhanced chemotherapy:Experimental biology and medicine (Maywood, N.J.) · 2020Article
- Low‑intensity ultrasound enhances the antitumor effects of doxorubicin on hepatocellular carcinoma cells through the ROS‑miR‑21‑PTEN axis.Molecular medicine reports · 2020Article
- Value of ultrasound combined with MRI in the diagnosis of primary and recurrent hepatocellular carcinoma.Oncology letters · 2019Article
- Caffeine enhances the anti-tumor effect of 5-fluorouracil via increasing the production of reactive oxygen species in hepatocellular carcinoma.Medical oncology (Northwood, London, England) · 2019Article
- Low‑intensity ultrasound enhances the chemosensitivity of hepatocellular carcinoma cells to cisplatin via altering the miR‑34a/c‑Met axis.International journal of molecular medicine · 2019Article
- Very low intensity ultrasounds as a new strategy to improve selective delivery of nanoparticles-complexes in cancer cells.Journal of experimental & clinical cancer research : CR · 2019Article
Corrections and comments
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Authors and funding
8 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundHepatocellular carcinoma (HCC) accounts for 75% of liver cancers and is the second most lethal cancer, associated with its multiple etiologies, poor prognosis and resistance to chemotherapy drugs. Chemotherapy treatment on HCC suffers low efficacy of drug uptake and can produce a range of side effects. Here we report an investigation on the effect of a combined treatment on human hepatocellular carcinoma BEL-7402 cells using low-intensity ultrasound (US) and 5-fluorouracil (5-FU).
methodsThe uptake of 5-FU was measured by the high-performance liquid chromatography (HPLC). DNA damage was detected by the comet assay. MTT assay was used to examine cell viability. Intracellular reactive oxygen species (ROS) and mitochondrial membrane potential (Δψm) were respectively detected by the fluorescent probes DCFH-DA or JC-1. Endogenous apoptosis-associated proteins were analyzed by the western blot and immunohistochemistry. Histopathological changes were evaluated by the hematoxylin and eosin (H&E) staining. Cell apoptosis was evaluated by the TUNEL and flow cytometry assays. Cell proliferation was measured using the immunohistochemical staining of PCNA.
resultsOur results showed that low-intensity US (1.1 MHz, 1.0 W/cm2, 10% duty cycle) significantly enhanced the uptake of 5-FU, 5-FU-mediated DNA damage and reactive oxygen species (ROS) generation. The increased ROS production up-regulated the p53 protein level, which led to the up-regulation of Bax and down-regulation of Bcl-2. The enhancement of ROS generation and the activation of the apoptosis-associated proteins further triggered the collapse of mitochondrial membrane potential, released cytochrome c from mitochondria into cytosol and activated the mitochondria-caspase pathway, and cell apoptosis. Such enhanced effects could be partially blocked by the ROS scavenger N-acetylcysteine (NAC). Overall, low-intensity US combined with 5-FU led to an effective inhibition of tumor growth and prolonged overall survival of BEL-7402 HCC-bearing nude mice by more than 15% compared with 5-FU treatment alone.
conclusionsOur results showed that low-intensity ultrasound combined with 5-FU produced much enhanced synergistic anti-tumor effects via enhanced ROS production in treating HCC.
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