ArticleBMC cancer2019
GX15-070 (Obatoclax), a Bcl-2 family proteins inhibitor engenders apoptosis and pro-survival autophagy and increases Chemosensitivity in neuroblastoma.
Article in BMC cancer, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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Who cites it
15 citing papers in PubMed, 28 citations in OpenAlex.
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- Genetic mutations affecting mitochondrial function in cancer drug resistance.Genes & genomics · 2023Review
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- Therapy resistance in neuroblastoma: Mechanisms and reversal strategies.Frontiers in pharmacology · 2023Review
- Global Effect of COVID-19 Pandemic on Cancer Patients and its Treatment: A Systematic Review.Clinical complementary medicine and pharmacology · 2022Review
- Increased MCL-1 synthesis promotes irradiation-induced nasopharyngeal carcinoma radioresistance via regulation of the ROS/AKT loop.Cell death & disease · 2022Article
- BH3-mimetics: recent developments in cancer therapy.Journal of experimental & clinical cancer research : CR · 2021Review
- Downregulation of HOXA11 enhances endometrial cancer malignancy and cisplatin resistance via activating PTEN/AKT signaling pathway.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2021Article
- Aberrant Bcl-x splicing in cancer: from molecular mechanism to therapeutic modulation.Journal of experimental & clinical cancer research : CR · 2021Review
- Review
- Integrated Genomic Profiling and Drug Screening of Patient-Derived Cultures Identifies Individualized Copy Number-Dependent Susceptibilities Involving PI3K Pathway and 17q Genes in Neuroblastoma.Frontiers in oncology · 2021Article
- The immuno-oncological challenge of COVID-19.Nature cancer · 2020Review
- Emerging therapeutic targets for neuroblastoma.Expert opinion on therapeutic targets · 2020Review
- The crosstalk between lncRNAs and the Hippo signalling pathway in cancer progression.Cell proliferation · 2020Review
Corrections and comments
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Authors and funding
10 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundNeuroblastoma (NB) is a frequent pediatric tumor associated with poor prognosis. The disregulation of Bcl-2, an anti-apoptotic protein, is crucial for the tumoral development and chemoresistance. Autophagy is also implicated in tumor cell survival and chemoresistance. The aim of our study was to demonstrate therapeutic efficiency of GX 15-070, a pan-Bcl-2 family inhibitor, used alone and in combination with conventional drugs or with hydroxychloroquine (HCQ), an autophagy inhibitor.
methodsFive neuroblastoma cell lines were tested for the cytotoxic activity of GX 15-070 alone or in combination with cisplatin, doxorubicin, HCQ or Z-VAD-FMK a broad-spectrum caspase inhibitor. Apoptosis and autophagy levels were studied by western-blot and FACS. Orthotopic injections were performed on NOD/LtSz-scid/IL-2Rgamma null mice that were treated with either GX 15-070 alone or in combination with HCQ.
resultsSynergistic cytotoxicity was observed for the drug combination in all of the 5 neuroblastoma cell lines tested, including MYCN amplified lines and in cancer stem cells. GX 15-070 significantly increased apoptosis and autophagy in neuroblastoma cells as evidenced by increased levels of the autophagy marker, LC3-II. Inhibition of autophagy by HCQ, further increased the cytotoxicity of this combinatorial treatment, suggesting that autophagy induced by these agent plays a cytoprotective role. In vivo, GX 15-070 combined with HCQ significantly decreased the growth of the tumor and the number of distant metastases.
conclusionsBased on the synergistic effect of HCQ and GX 15-070 observed in this study, the combination of these two drugs may be utilized as a new therapeutic approach for neuroblastoma.
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