Establishment of a mouse ovarian cancer and peritoneal metastasis model to study intraperitoneal chemotherapy
- Intraperitoneal chemotherapy (IPC) is a locoregional treatment option in patients with peritoneal metastases (PM). Here, we present an ovarian cancer (OC)-derived PM mouse model for the study of different forms of IPC. Xenograft cell proliferation (luciferase-transfected OVCAR3 and SKOV3 clones) and growth kinetics were assessed using PET scan, bioluminescence imaging (BLI), and histological tumor analysis. Liquid IPC was achieved by intraperitoneal injection with/without capnoperitoneum (6–7 mmHg). Pressurized intraperitoneal aerosol chemotherapy (PIPAC) was mimicked using an intratracheal drug aerosol administration system (micro-nozzle), which, as demonstrated by ex vivo granulometric analysis using laser diffraction spectrometry, produced a polydisperse, bimodal aerosol with a volume-weighted median diameter of (26.49 \(\pm\) 2.76) µm. Distribution of Tc-99m-labeled doxorubicin in mice was characterized using SPECT and was dependent on the delivery mode and most homogeneous when the micro-nozzle was used. A total of 2 mg doxorubicin per kg body weight was determined to be the optimally effective and tolerable dose to achieve at least 50% tumor reduction. Repeated PIPAC (four times at seven-day-intervals) with doxorubicin in SKOV3-luc tumor-bearing mice resulted in halted tumor proliferation and tumor load reduced after the second round of PIPAC versus controls and the number of tumor nodules was significantly reduced (27.7 \(\pm\) 9.5 vs. 57.3 \(\pm\) 9.5; \(\it p\) = 0.0003). Thus, we established the first mouse model of OC PM for the study of IPC using a human xenograft with SKOV3 cells and an experimental IPC setup with a miniaturized nozzle. Repeated IPC was feasible and demonstrated time-dependent anti-tumor activity.
Author: | Günther RezniczekORCiDGND, Jonathan BuggischGND, Julien SobiloORCiDGND, Alexandre LaunayORCiDGND, Stephanie LerondelGND, Alain Le PapeGND, Mehdi OuaissiORCiDGND, Daniel GöhlerORCiDGND, Metin SenkalGND, Urs PabstGND, Clemens TempferORCiDGND |
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URN: | urn:nbn:de:hbz:294-79125 |
DOI: | https://doi.org/10.3390/cancers12123818 |
Parent Title (English): | Cancers |
Publisher: | MDPI |
Place of publication: | Basel |
Document Type: | Article |
Language: | English |
Date of Publication (online): | 2021/02/26 |
Date of first Publication: | 2020/12/17 |
Publishing Institution: | Ruhr-Universität Bochum, Universitätsbibliothek |
Tag: | Open Access Fonds aerosol; chemotherapy; intraperitoneal; metastasis; mouse model; ovarian cancer; peritoneal; pressurized |
Volume: | 12 |
Issue: | 12, Artikel 3818 |
First Page: | 3818-1 |
Last Page: | 3818-13 |
Note: | Article Processing Charge funded by the Deutsche Forschungsgemeinschaft (DFG) and the Open Access Publication Fund of Ruhr-Universität Bochum. |
Institutes/Facilities: | Marienhospital Herne, Klinik für Frauenheilkunde und Geburtshilfe |
Dewey Decimal Classification: | Technik, Medizin, angewandte Wissenschaften / Medizin, Gesundheit |
Licence (English): | Creative Commons - CC BY 4.0 - Attribution 4.0 International |