FOXM1 Inhibition in Ovarian Cancer Tissue Cultures Affects Individual Treatment Susceptibility Ex Vivo
1
Institute of Anatomy, University of Leipzig, Liebigstr. 13, 04103 Leipzig, Germany
2
Department of Gynecology, University of Leipzig Medical Center, Liebigstr. 20a, 04103 Leipzig, Germany
3
University Cancer Center Leipzig (UCCL), University of Leipzig Medical Center, Liebigstr. 22, 04103 Leipzig, Germany
4
Institute of Pathology, University of Leipzig Medical Center, Liebigstr. 26, 04103 Leipzig, Germany
5
Department of Oncology, University of Leipzig Medical Center, Liebigstr. 22, 04103 Leipzig, Germany
*
Author to whom correspondence should be addressed.
Academic Editors: Krzysztof Ksiązek and Xianjun Fang
Cancers 2021, 13(5), 956; https://doi.org/10.3390/cancers13050956
Received: 11 January 2021 / Revised: 3 February 2021 / Accepted: 22 February 2021 / Published: 25 February 2021
(This article belongs to the Special Issue Molecular Biology of Ovarian Cancer: From Mechanisms of Intraperitoneal Metastasis to Therapeutic Opportunities)
Simple Summary
Late diagnosis of ovarian cancer is a major reason for the high mortality rate of this tumor entity. The time to determine tumor susceptibility to treatment is scarce and resistance to therapy occurs very frequently. Here, we aim for a model system that can determine tumor response to (I) study novel drugs and (II) enhance patient stratification. Tissue specimens (n = 10) were acquired from fresh surgical samples. Tissue cultures were cultivated and treated with clinically relevant therapeutics and an FOXM1 inhibitor for 3–6 days. The transcription factor FOXM1 is a key regulator of tumor survival affecting multiple cancerogenic target genes. Gene expression of FOXM1 and its targets BRCA1/2 and RAD51 were investigated together with tumor susceptibility. Tissue cultures successfully demonstrated the individual benefit of FOXM1 inhibition and revealed the potency of the complex model system for oncological research.
Diagnosis in an advanced state is a major hallmark of ovarian cancer and recurrence after first line treatment is common. With upcoming novel therapies, tumor markers that support patient stratification are urgently needed to prevent ineffective therapy. Therefore, the transcription factor FOXM1 is a promising target in ovarian cancer as it is frequently overexpressed and associated with poor prognosis. In this study, fresh tissue specimens of 10 ovarian cancers were collected to investigate tissue cultures in their ability to predict individual treatment susceptibility and to identify the benefit of FOXM1 inhibition. FOXM1 inhibition was induced by thiostrepton (3 µM). Carboplatin (0.2, 2 and 20 µM) and olaparib (10 µM) were applied and tumor susceptibility was analyzed by tumor cell proliferation and apoptosis in immunofluorescence microscopy. Resistance mechanisms were investigated by determining the gene expression of FOXM1 and its targets BRCA1/2 and RAD51. Ovarian cancer tissue was successfully maintained for up to 14 days ex vivo, preserving morphological characteristics of the native specimen. Thiostrepton downregulated FOXM1 expression in tissue culture. Individual responses were observed after combined treatment with carboplatin or olaparib. Thus, we successfully implemented a complex tissue culture model to ovarian cancer and showed potential benefit of combined FOXM1 inhibition.
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Keywords:
ovarian cancer; FOXM1; tissue culture; resistance; homologous recombination (HR); susceptibility; olaparib; carboplatin; thiostrepton
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MDPI and ACS Style
Brückner, L.; Reinshagen, A.; Hoang, N.A.; Höhn, A.K.; Lordick, F.; Bechmann, I.; Aktas, B.; Nel, I.; Kallendrusch, S. FOXM1 Inhibition in Ovarian Cancer Tissue Cultures Affects Individual Treatment Susceptibility Ex Vivo. Cancers 2021, 13, 956. https://doi.org/10.3390/cancers13050956
AMA Style
Brückner L, Reinshagen A, Hoang NA, Höhn AK, Lordick F, Bechmann I, Aktas B, Nel I, Kallendrusch S. FOXM1 Inhibition in Ovarian Cancer Tissue Cultures Affects Individual Treatment Susceptibility Ex Vivo. Cancers. 2021; 13(5):956. https://doi.org/10.3390/cancers13050956
Chicago/Turabian StyleBrückner, Luzie; Reinshagen, Annika; Hoang, Ngoc A.; Höhn, Anne K.; Lordick, Florian; Bechmann, Ingo; Aktas, Bahriye; Nel, Ivonne; Kallendrusch, Sonja. 2021. "FOXM1 Inhibition in Ovarian Cancer Tissue Cultures Affects Individual Treatment Susceptibility Ex Vivo" Cancers 13, no. 5: 956. https://doi.org/10.3390/cancers13050956
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