ArticleMolecular and cellular biochemistry2016
Hypoxia-induced resistance to cisplatin-mediated apoptosis in osteosarcoma cells is reversed by gambogic acid independently of HIF-1α.
Article in Molecular and cellular biochemistry, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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Who cites it
12 citing papers in PubMed, 21 citations in OpenAlex.
- Comprehensive investigation of hypoxia-associated genes and their predictive significance in osteosarcoma.Translational oncology · 2026Article
- The role of cisplatin in modulating the tumor immune microenvironment and its combination therapy strategies: a new approach to enhance anti-tumor efficacy.Annals of medicine · 2025Review
- Development of a ratiometric fluorescence nanosensor for evaluating precision chemotherapy of osteosarcoma through real-time monitoring of caspase-3 activity.Mikrochimica acta · 2025Article
- The Role of Nutraceuticals in Chemoprevention and their Therapeutic Effects when used in Combination with Synthetic Drugs.Current medicinal chemistry · 2025Review
- Recent Insights into Therapy Resistance in Osteosarcoma.Cancers · 2020Review
- Gambogic Acid as a Candidate for Cancer Therapy: A Review.International journal of nanomedicine · 2020Review
- HIF2A overexpression reduces cisplatin sensitivity in cervical cancer by inducing excessive autophagy.Translational cancer research · 2020Article
- New Insights into Mechanisms of Cisplatin Resistance: From Tumor Cell to Microenvironment.International journal of molecular sciences · 2019Review
- Angiopoietin-like protein 2 is an important facilitator of tumor proliferation, metastasis, angiogenesis and glycolysis in osteosarcoma.American journal of translational research · 2019Article
- Hypoxia-mediated mitochondria apoptosis inhibition induces temozolomide treatment resistance through miR-26a/Bad/Bax axis.Cell death & disease · 2018Article
- Bufalin induces DNA damage response under hypoxic condition in myeloma cells.Oncology letters · 2018Article
- P2YFrontiers in pharmacology · 2018Review
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
In vitro evidence of hypoxia-induced resistance to cisplatin (CDDP)-mediated apoptosis exists in human osteosarcoma (OS). Gambogic acid (GA) is a promising chemotherapeutic compound that could increase the chemotherapeutic effectiveness of CDDP in human OS cells by inducing cell cycle arrest and promoting apoptosis. This study examined whether GA could overcome OS cell resistance to CDDP. Hypoxia significantly reduced levels of CDDP-induced apoptosis in the OS cell lines MG63 and HOS. However, combined treatment with GA and CDDP revealed a strong synergistic action between these drugs, and higher protein levels of the apoptosis-related factor Fas, cleaved caspase-8 and cleaved caspase-3 and lower expression of hypoxia-inducible factor (HIF)-1α are detected in both cell lines. Meanwhile, drug resistance was not reversed by exposure to the HIF-1α inhibitor 2-methoxyestradiol. These findings strongly suggest that hypoxia-induced resistance to CDDP is reversed by GA in OS cells independently of HIF-1α. Furthermore, in vivo studies using xenograft mouse models revealed that combination therapy with CDDP and GA exerted increased antitumor effects by inducing apoptosis. Taken together, our results demonstrate that GA may be a new potent therapeutic agent useful for targeting human OS cells.
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