{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,8]],"date-time":"2026-09-08T00:00:28Z","timestamp":1788825628035,"version":"build-2803163510"},"reference-count":38,"publisher":"Bioscientifica","issue":"2","content-domain":{"domain":["erc.bioscientifica.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2023,2,1]]},"abstract":"<jats:p>\n                    The pharmacological approach to adrenocortical carcinoma (ACC) is based on mitotane with\/without etoposide, doxorubicin, and cisplatin, according to the disease stage. Considering the limited efficacy and toxicity of this treatment, new strategies are required. Trabectedin is a marine-derivated antitumoral agent that inhibits oncogenic transcription. We have already demonstrated trabectedin cytotoxic activity at sub-nanomolar concentrations in ACC cells. Here, we expanded the investigation of trabectedin effect on ACC preclinical models, evaluating whether trabectedin could affect ACC cells\u2019 invasiveness and metastasis formation. NCI-H295R, MUC-1, and TVBF-7 cell lines were used. Cell tumor xenografts in Danio rerio embryos were performed. The tumor mass areas and the number of embryos with metastasis were evaluated. The\n                    <jats:italic>in vitro<\/jats:italic>\n                    invasiveness of cells was evaluated. Effects of trabectedin of\n                    <jats:italic>MMP2<\/jats:italic>\n                    ,\n                    <jats:italic>TIMP1<\/jats:italic>\n                    , and\n                    <jats:italic>TIMP2<\/jats:italic>\n                    were evaluated at gene level qRT-PCR. MMP2 secreted in the cell medium was evaluated by Western blot and by zymography. Xenograft experiments demonstrated that trabectedin significantly reduced the tumor area in each ACC cell model and metastasis formation in embryos injected with metastasis-derived cell lines. Trabectedin treatment reduced the invasiveness of ACC cells across the matrix, which was greater at baseline for the metastatic models. In metastatic cell models, protein analysis demonstrated a reduction of MMP2 secretion and activity in the culture medium after treatment. Our results indicate that trabectedin interferes with invasiveness and metastasis processes, both dramatic features of ACC. Furthermore, these results support those previously published in providing the rationale for a clinical evaluation of the efficacy of trabectedin in ACC patients.\n                  <\/jats:p>","DOI":"10.1530\/erc-22-0273","type":"journal-article","created":{"date-parts":[[2022,11,30]],"date-time":"2022-11-30T13:45:50Z","timestamp":1669815950000},"update-policy":"https:\/\/doi.org\/10.1530\/crossmarkpolicy-8","source":"Crossref","is-referenced-by-count":9,"title":["Trabectedin impairs invasiveness and metastasis in adrenocortical carcinoma preclinical models"],"prefix":"10.1530","volume":"30","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0835-0916","authenticated-orcid":true,"given":"Andrea","family":"Abate","sequence":"first","affiliation":[{"name":"Section of Pharmacology, Department of Molecular and Translational Medicine, University of Brescia, Brescia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mariangela","family":"Tamburello","sequence":"additional","affiliation":[{"name":"Section of Pharmacology, Department of Molecular and Translational Medicine, University of Brescia, Brescia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elisa","family":"Rossini","sequence":"additional","affiliation":[{"name":"Section of Pharmacology, Department of Molecular and Translational Medicine, University of Brescia, Brescia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ram Manohar","family":"Basnet","sequence":"additional","affiliation":[{"name":"Section of Pharmacology, Department of Molecular and Translational Medicine, University of Brescia, Brescia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giovanni","family":"Ribaudo","sequence":"additional","affiliation":[{"name":"Section of Pharmacology, Department of Molecular and Translational Medicine, University of Brescia, Brescia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alessandra","family":"Gianoncelli","sequence":"additional","affiliation":[{"name":"Section of Pharmacology, Department of Molecular and Translational Medicine, University of Brescia, Brescia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Constanze","family":"Hantel","sequence":"additional","affiliation":[{"name":"Department of Endocrinology, Diabetology and Clinical Nutrition, University Hospital Zurich (USZ) and University of Zurich (UZH), Zurich, Switzerland"},{"name":"Medizinische Klinik und Poliklinik III, University Hospital Carl Gustav Carus Dresden, Dresden, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Deborah","family":"Cosentini","sequence":"additional","affiliation":[{"name":"Oncology Unit, Department of Medical and Surgical Specialties, Radiological Sciences and Public Health, University of Brescia and ASST Spedali Civili di Brescia, Brescia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marta","family":"Lagan\u00e0","sequence":"additional","affiliation":[{"name":"Oncology Unit, Department of Medical and Surgical Specialties, Radiological Sciences and Public Health, University of Brescia and ASST Spedali Civili di Brescia, Brescia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Salvatore","family":"Grisanti","sequence":"additional","affiliation":[{"name":"Oncology Unit, Department of Medical and Surgical Specialties, Radiological Sciences and Public Health, University of Brescia and ASST Spedali Civili di Brescia, Brescia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guido Alberto Massimo","family":"Tiberio","sequence":"additional","affiliation":[{"name":"Surgical Clinic, Department of Clinical and Experimental Sciences, University of Brescia at ASST Spedali Civili di Brescia, Brescia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maurizio","family":"Memo","sequence":"additional","affiliation":[{"name":"Section of Pharmacology, Department of Molecular and Translational Medicine, University of Brescia, Brescia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alfredo","family":"Berruti","sequence":"additional","affiliation":[{"name":"Oncology Unit, Department of Medical and Surgical Specialties, Radiological Sciences and Public Health, University of Brescia and ASST Spedali Civili di Brescia, Brescia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sandra","family":"Sigala","sequence":"additional","affiliation":[{"name":"Section of Pharmacology, Department of Molecular and Translational Medicine, University of Brescia, Brescia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"416","reference":[{"key":"bib1","series-title":"Cancers (Basel)","article-title":"Cytotoxic effect of 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(https:\/\/doi.org\/10.1210\/jc.2016-2414)"},{"key":"bib15","series-title":"Journal of Oncology","article-title":"Molecular drivers of potential immunotherapy failure in adrenocortical carcinoma","volume":"2019","author":"Fiorentini","year":"2019","unstructured":"Fiorentini CGrisanti SCosentini DAbate ARossini EBerruti ASigala S2019Molecular drivers of potential immunotherapy failure in adrenocortical carcinoma. Journal of Oncology2019 6072863. (https:\/\/doi.org\/10.1155\/2019\/6072863)"},{"key":"bib16","series-title":"Anticancer Research","first-page":"913","article-title":"Inhibition of survivin is associated with zoledronic acid-induced apoptosis of prostate cancer cells","volume":"36","author":"Fragni","year":"2016","unstructured":"Fragni MBonini SAStabile ABodei SCristinelli LSimeone CZani DSpano PFBerruti AMemo M2016Inhibition of survivin is associated with zoledronic acid-induced apoptosis of prostate cancer cells. Anticancer Research36913\u2013920."},{"key":"bib17","series-title":"Molecular and Cellular Endocrinology","article-title":"In vitro cytotoxicity of cabazitaxel in adrenocortical carcinoma cell lines and human adrenocortical carcinoma primary cell cultures\u2606","volume":"498","author":"Fragni","year":"2019","unstructured":"Fragni MPalma Lopez LPRossini EAbate ACosentini DSalvi VVezzoli SPoliani PLBosisio DHantel C2019In vitro cytotoxicity of cabazitaxel in adrenocortical carcinoma cell lines and human adrenocortical carcinoma primary cell cultures\u2606. Molecular and Cellular Endocrinology498 110585. 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