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Updated: Mar 22, 2026
A Doxorubicin-induced Cardiomyopathy Model in Adult Zebrafish
Published on: June 7, 2018
[Effect of Doxorubicin on abcb4 Gene Expression in Zebrafish (Danio rerio) Embryos]
Objective:
To determine the effect of doxorubicin (DOX) on abcb4 gene expression and the role of abcb4 gene in multidrug-resistance.
Methods:
Zebrafish embryos were treated with 2 mL/L DMSO, 10 μmol/L DOX and 2 mL/L DMSO+10 μmol/L DOX, respectively. The zebrafish embryos treated with Eggwater served as controls. Exposures started at 4 to 16 cell stage of the embryos and terminated 120 hours post fertilization (hpf). The expression of abcb4 gene in zebrafish embryos was examined on 48, 72, 96, and 120 hpf with whole-mount in situ hybridization (WISH) and quantitative real-time PCR (qPCR).
Results:
Compared with the controls, DOX-exposed embryos had higher level of abcb4 gene expression (P < 0.05), but not for abcb5 gene. WISH showed that abcb4 gene was expressed in the guts of zebrafish embryos. However, those exposed to DOX also showed strong WISH signals in the brain and heart.
Conclusion:
Doxorubicin increases the expression of abcb4 gene in zebrafish embryos. abcb4 gene may play an imoortant role in multidrug-resistance.
Insights
Doxorubicin (DOX) exposure significantly increased abcb4 gene expression in zebrafish embryos. This suggests the abcb4 gene plays a crucial role in multidrug resistance, offering insights into cancer treatment resistance mechanisms.
Area of Science:
- Molecular Biology
- Developmental Biology
- Pharmacology
Background:
- Multidrug resistance (MDR) is a major challenge in cancer chemotherapy.
- Understanding the genetic basis of MDR is crucial for developing effective treatment strategies.
- The abcb4 gene, a member of the ATP-binding cassette transporter superfamily, is implicated in drug efflux.
Purpose of the Study:
- To investigate the impact of doxorubicin (DOX) on abcb4 gene expression in zebrafish embryos.
- To explore the potential role of the abcb4 gene in conferring multidrug resistance.
Main Methods:
- Zebrafish embryos were exposed to DOX at various concentrations.
- Gene expression levels of abcb4 were analyzed using whole-mount in situ hybridization (WISH) and quantitative real-time PCR (qPCR) at multiple time points post-fertilization.
- Expression patterns were examined in different embryonic tissues.
Main Results:
- Doxorubicin exposure led to a significant upregulation of abcb4 gene expression compared to controls (P < 0.05).
- No significant change was observed in abcb5 gene expression.
- WISH analysis revealed abcb4 expression in the gut, with enhanced signals in the brain and heart upon DOX treatment.
Conclusions:
- Doxorubicin treatment effectively increases abcb4 gene expression in zebrafish embryos.
- The abcb4 gene is a potential key player in the development of multidrug resistance, warranting further investigation.
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