ArticleJournal of molecular medicine (Berlin, Germany)2013
Inhibition of autophagy enhances anticancer effects of bevacizumab in hepatocarcinoma.
Article in Journal of molecular medicine (Berlin, Germany), 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 57 papers.
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Who cites it
57 citing papers in PubMed, 107 citations in OpenAlex.
- Autophagy-related polymorphisms predict hypertension in patients with metastatic colorectal cancer treated with FOLFIRI and bevacizumab: Results from TRIBE and FIRE-3 trials.European journal of cancer (Oxford, England : 1990) · 2017Trial
- Dual regulation of autophagy: paradoxical effects on tumor angiogenesis.Frontiers in cell and developmental biology · 2026Review
- 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
- Review
- Simultaneous activation and blockade of autophagy to fight hepatocellular carcinoma.Autophagy reports · 2024Article
- Article
- Autophagy: A challengeable paradox in cancer treatment.Cancer medicine · 2023Review
- Nanotherapeutics in autophagy: a paradigm shift in cancer treatment.Drug delivery and translational research · 2022Review
- Naturally Occurring Antioxidant Therapy in Alzheimer's Disease.Antioxidants (Basel, Switzerland) · 2022Review
- Myricetin Induces Apoptosis and Protective Autophagy through Endoplasmic Reticulum Stress in Hepatocellular Carcinoma.Evidence-based complementary and alternative medicine : eCAM · 2022Article
- Blockade of Uttroside B-Induced Autophagic Pro-Survival Signals Augments Its Chemotherapeutic Efficacy Against Hepatocellular Carcinoma.Frontiers in oncology · 2022Article
- Autophagy deficiency downregulates OAging · 2021Article
- A novel hypoxia gene signature indicates prognosis and immune microenvironments characters in patients with hepatocellular carcinoma.Journal of cellular and molecular medicine · 2021Article
- Novel Ferrocene Derivatives Induce G0/G1 Cell Cycle Arrest and Apoptosis through the Mitochondrial Pathway in Human Hepatocellular Carcinoma.International journal of molecular sciences · 2021Article
- Combining Everolimus and Ku0063794 Promotes Apoptosis of Hepatocellular Carcinoma Cells via Reduced Autophagy Resulting from Diminished Expression of miR-4790-3p.International journal of molecular sciences · 2021Article
- Hypoxia-Induced Autophagy Enhances Cisplatin Resistance in Human Bladder Cancer Cells by Targeting Hypoxia-Inducible Factor-1Journal of immunology research · 2021Article
- Targeting autophagy to overcome drug resistance: further developments.Journal of hematology & oncology · 2020Review
- Adaptive response of resistant cancer cells to chemotherapy.Cancer biology & medicine · 2020Review
- Morin Hydrate Sensitizes Hepatoma Cells and Xenograft Tumor towards Cisplatin by Downregulating PARP-1-HMGB1 Mediated Autophagy.International journal of molecular sciences · 2020Article
- Autophagy as a mechanism for anti-angiogenic therapy resistance.Seminars in cancer biology · 2020Review
Corrections and comments
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Authors and funding
12 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Angiogenesis inhibitors have long been considered desirable anticancer agents. However, it was found that many tumors could develop resistance to antiangiogenesis inhibitors. Antiangiogenic therapy results in metabolic stress. Autophagy is an important survival mechanism in cancer cells under metabolic stress; however, it remains unknown if autophagy contributes to antiangiogenesis resistance. In this study, we reported that bevacizumab treatment reduced the development of new blood vessels and inhibited cell growth in xenografts of hepatocellular carcinoma (HCC) tumors. Bevacizumab treatment also upregulated expression of the autophagy-related genes (Beclin1 and LC3) and increased autophagosome formation. Our in vitro studies demonstrated that autophagy inhibition significantly increased apoptosis of HCC cells during nutrient starvation or hypoxia. In addition, the combined treatment of an autophagy inhibitor and bevacizumab markedly inhibited the tumor growth of HCC xenografts, led to enhanced apoptosis, and impaired the proliferation of tumor cells compared with treatment with either drug alone. Furthermore, autophagy inhibition led to enhanced reactive oxygen species (ROS) generation in HCC cells exposed to nutrient starvation or hypoxia in vitro and increased DNA oxidative damage in vivo. Antioxidants reduced nutrient starvation or the hypoxia-induced cell death of HCC cells after autophagy inhibition. Our results suggest that autophagy modulates ROS generation and contributes to cell survival under metabolic stress. Therefore, autophagy inhibition may be a novel way of increasing the efficicacy of antiangiogenic agents in the treatment of HCC.
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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.