PUBLICATION
Adrenocortical carcinoma xenograft in zebrafish embryos as model to study the in vivo cytotoxicity of abiraterone acetate
- Authors
- Gianoncelli, A., Guarienti, M., Fragni, M., Bertuzzi, M., Rossini, E., Abate, A., Basnet, R.M., Zizioli, D., Bono, F., Terzolo, M., Memo, M., Berruti, A., Sigala, S.
- ID
- ZDB-PUB-190810-7
- Date
- 2019
- Source
- Endocrinology 160(11): 2620-2629 (Journal)
- Registered Authors
- Keywords
- none
- MeSH Terms
-
- Abiraterone Acetate/therapeutic use*
- Adrenocortical Carcinoma/drug therapy*
- Animals
- Antineoplastic Agents/therapeutic use*
- Cell Line, Tumor
- Humans
- Xenograft Model Antitumor Assays
- Zebrafish
- PubMed
- 31397841 Full text @ Endocrinology
Citation
Gianoncelli, A., Guarienti, M., Fragni, M., Bertuzzi, M., Rossini, E., Abate, A., Basnet, R.M., Zizioli, D., Bono, F., Terzolo, M., Memo, M., Berruti, A., Sigala, S. (2019) Adrenocortical carcinoma xenograft in zebrafish embryos as model to study the in vivo cytotoxicity of abiraterone acetate. Endocrinology. 160(11):2620-2629.
Abstract
Purpose Abiraterone acetate (AbiAc) inhibits tumor growth when administered to immunodeficient mice engrafted with in vitro cell model of human adrenocortical carcinoma (ACC). Here, we developed and validated a zebrafish model engrafted with cortisol-secreting ACC cells to study the effects of AbiAc on tumor growth.
Methods The experimental conditions for AbiAc absorption in AB zebrafish embryos as embryos number, AbiAc concentrations and absorption time-curve by LC-MS/MS were set up. The AbiAc effect on steroid production in AB zebrafish embryos was as well measured. ACC cells (NCI-H295R cell line, the primary cells ACC29 and the negative control cells SW13) were treated with the Dili fluorescent dye and about 240 cells/4 nl were injected in the subperidermal space of the yolk sac of AB zebrafish embryos (n=80±10). Cell area was measured with Noldus DanioScopeTM software.
Results AbiAc absorption in AB zebrafish embryos was stage-dependent. Abiraterone (Abi) concentration decreased while its main metabolite, namely Δ4A, increased. Accordingly, we demonstrated that zebrafish expressed the enzyme 3β-hydroxysteroid dehydrogenase mRNA, that converts Abi in Δ4A. Furthermore, ABiAc reduced zebrafish embryos cortisol production and increased progesterone. Three days after cell injection (T3), the cortisol-secreting ACC cell area in solvent-treated embryos was significantly higher compared to 1 µM AbiAC-treated embryos, while no AbiAc effect was observed in SW13, that lacks the Abi target enzyme CYP17A1.
Conclusions Zebrafish embryo xenografted with ACC tumor cells could be a useful, fast and reproducible experimental model to preclinically test the activity of new drugs potentially active in human ACC.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping