LIFE SCIENCES
·
2025
·
IF 5.1
Wenwen Zha,Ziang Wang,Weitao Hu,Chenkai Ge,Wenbin Yuan,Qinyuan Shen,Weirong Li,Wanqing Chen,Jingrong Tang,Zhonghao Xiao,Yunlong Meng,Lirong Huang,Zilin Zhong,Tao-Sheng Li,Jianjun Chen,Zigang Cao
Bexarotene (Bex) is a selective retinoid X receptor (RXR) agonist and is commonly used as an anti-tumor drug in the clinic to treat patients with cutaneous T-cell lymphoma (CTCL). With the widespread use of this drug, people are increasingly concerned about its side effects and safety of use. At present, the effects of bexarotene drugs on the health of organisms remain uncertain, but retinoid drugs are generally biologically active and may pose potential risks to them. Therefore, in this study, we used a zebrafish model to evaluate the effects of Bex on embryonic development. Six hours after fertilization, we exposed zebrafish embryos to 3 μg/L, 6 μg/L, and 9 μg/L bexarotene. At 96 hpf, compared with the control group, zebrafish embryos exposed to bexarotene showed obvious heart and liver development defects, including reduced hatching rate, pericardial enlargement, heart rate disorder, yolk sac edema, small liver area and abnormal photo-optical motor responses. Transcriptome and qPCR results showed abnormal expression of genes related to heart and liver development was induced by Bexarotene. Mechanistically, bexarotene induced a significant upregulation of the transcriptional expression levels of genes related to the Wnt signaling pathway, and IWR-1 was able to effectively rescue the heart and liver developmental defects of zebrafish caused by bexarotene. Therefore, our study showed that bexarotene may cause zebrafish embryonic developmental defects by upregulating the Wnt signaling pathway, revealing the side effects and associated novel mechanisms of bexarotene, and providing a theoretical basis for its safe and effective use in the treatment of clinically related diseases.
研究领域:
发育生物学
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毒理学
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分子生物学
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产品关联
DOI
PubMed
高影响因子
BIOMEDICINE & PHARMACOTHERAPY
·
2026
·
IF 7.5
Wenwen Zha,Minglei Wang,Yunlong Meng,Kangyu Liu,Lirong Huang,Haining Li,Nan Yin,Yuanhai Xie,Jiayi Du,Mingxia Song,Zigang Cao,Jianjun Chen,Zilin Zhong
Bexarotene is a retinoid X receptor (RXR) agonist that plays a crucial role in cell growth and differentiation. It has shown potential in treating both early- and late-stage cutaneous T-cell lymphoma (CTCL). However, the impact of Bexarotene on the neurodevelopment of aquatic organisms, particularly aquatic vertebrates, remains poorly understood. This study aimed to investigate the effects of various concentrations of bexarotene (3 μg/L, 6 μg/L, and 9 μg/L) on the development of the zebrafish embryonic nervous system, using zebrafish as a model organism. The underlying molecular mechanisms were explored through a combination of pharmacological interventions, molecular biology, histopathology, and transcriptomics. Studies have shown that zebrafish embryos exposed to Bex show significant changes in development, including morphological abnormalities, head malformations, significantly shortened head length and width, reduced fluorescent area, cell apoptosis, shortened spinal motor neuron axon length, abnormal myelin development, decreased oligodendrocytes, cerebellar developmental damage, and abnormal behavior. Transcriptomics and qPCR results showed abnormal expression of neurodevelopmental genes ( olig2 , mbpa , atoh1a , gfap , ngn1 , gap43 , etc.). In addition, exposure to medium and high concentrations of bexarotene significantly increased acetylcholinesterase (AChE) activity. Bexarotene activates the Wnt signaling pathway, and treatment with the Wnt inhibitor IWR-1 can partially rescue the neurodevelopmental impairments in embryos. In summary, bexarotene offers new insights into the potential neurodevelopmental risks in zebrafish embryos, emphasizing the importance of preventing drug side effects and ensuring the safe and rational use of medications to protect the health of living organisms.
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产品关联
DOI
PubMed
高影响因子
BMC CANCER
·
2018
·Vol. 18
·期 1
·1-10
·
IF 3.288
Ai Xinghao,Mao Feng,Shen Shengping,Shentu Yang,Wang Jiejun,Lu Shun
Background Thirty to 40 % of non-small cell lung cancer (NSCLC) patients developed higher hypertriglyceridemia in the process of treatment with bexarotene. And bioinformatics studies discovered that the expression of slc10a2 was increased in high-grade hypertriglyceridemia patients. So, we will explore the mechanism which may involve in this process.Methods We constructed slc10a2 overexpressed A549 cells and H1299 cells as cell models, normal A549 cells and H1299 cells as control. Then we explored the effects of slc10a2 on A549 cells and H1299 cells behaviors, including proliferation, invasion and apoptosis. The expression of apoptotic related genes and anti-cancer genes also been detected.Results We found that the proliferation and migration were inhibited and the apoptosis of NSCLC cells was accelerated by bexarotene. In addition, overexpressed slc10a2 in NSCLC cells can further suppress the proliferation and migration, and promote apoptosis under the treatment of bexarotene. On the contrary, the opposite results were obtained after slc10a2 gene was silenced in NSCLC cells treated with bexarotene. Moreover, the expression of caspase 3, caspase 7, PTEN, P21, P53, LKB1, TSC2 were increased and the expression of Bcl-2, cyclin D1, c-FLIP were declined in NSCLC cells and slc10a2 overexpressed NSCLC cells with the treatment of bexarotene, and the opposite situations were seen after slc10a2 gene was silenced in NSCLC cells. The further studies revealed the increased expression of slc10a2 activated the expression of peroxisome proliferator-activated receptor γ (PPARγ), then up-regulated PTEN expression and down-regulated mTOR expression.Conclusion These results suggest that bexarotene inhibits the viability of lung cancer cells via slc10a2/PPARγ/PTEN/mTOR signaling pathway.
研究领域:
肿瘤学
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分子生物学
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药理学
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DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF PHARMACEUTICS
·
2023
·
IF 5.8
Yihui Yang,Mingchao Yu,Liwen Ren,Qi An,Wan Li,Hong Yang,Yizhi Zhang,Sen Zhang,Yue Hao,Guanhua Du,Dezhi Yang,Yang Lu,Jinhua Wang
Psoriasis is a common systemic inflammatory skin disorder affecting over 60 million people globally. Some patients with psoriasis are associated with a higher risk of type 2 diabetes mellitus (T2DM). Psoriasis and T2DM occur concurrently in some patients; however, there is no effective drug for the treatment of psoriasis with T2DM. Bexarotene (BEX) is a specific RXR agonist and an antineoplastic agent indicated by the FDA for cutaneous T-cell lymphoma (CTLA). Metformin (MET) is the first-line treatment for T2DM. To develop novel effective drugs for the treatment of psoriasis with T2DM, multicomponent salts containing MET and BEX were designed and synthesized based on the drug–drug combination strategy. MET-BEX (1:1) and MET-BEX-H 2 O (1:1:1) were obtained and structurally characterized. The in vitro evaluation results showed that the hygroscopicity of MET was significantly optimized by the salt formation strategy, while the solubility of BEX was improved, which laid the foundation for improving the bioavailability of BEX in vivo . In a mouse model of imiquimod-induced psoriasis with T2DM, MET-BEX ameliorated imiquimod-induced psoriasis morphological features and systematic inflammation and improved glucolipid metabolism. These results showed that the multicomponent drug combination strategy in this study optimized the physicochemical properties of MET and BEX simultaneously, providing a promising candidate therapy for psoriasis with T2DM.
研究领域:
药学
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药理学
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皮肤科
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内分泌学
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药物设计与开发
✓ 已验证
DOI
PubMed
高影响因子
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