期刊
CANCER LETTERS
卷 421, 期 -, 页码 51-58出版社
ELSEVIER IRELAND LTD
DOI: 10.1016/j.canlet.2018.02.006
关键词
Ovarian cancer; Proliferation; Apoptosis; Chemotherapy; Ex vivo explant assay
类别
资金
- Ovarian Cancer Research Foundation (OCRF), Australia
- Lin Huddleston Ovarian Cancer Fellowship - Cancer Council South Australia
- Adelaide Medical School, University of Adelaide
- OvCan scholarship from The Royal Australian and New Zealand of Obstetricians and Gynaecologists (RANZCOG)
The majority of ovarian cancer patients present with advanced disease and despite aggressive treatment, prognosis remains poor. Response to first-line carboplatin-containing chemotherapy is usually good, however, recurrence rates and subsequent chemoresistance are very high and ultimately responsible for the fatal outcome of the disease. To improve treatment outcomes pre-clinical models that can predict individual patient response to 1st line chemotherapy and novel therapeutics are urgently required. In this study, we employed an ex vivo ovarian cancer tissue explant assay to assess response to carboplatin and an inhibitor of the extracellular matrix molecule, hyaluronan (4-methylubelliferone, 4-MU), shown to inhibit cancer metastasis. Cryopreserved ovarian cancer tissues were cultured on gelatine sponges for 48-120 h with increasing concentrations of carboplatin (0-400 mu M) or 4-MU (1 mM) alone or the combination of both drugs. Effects on apoptosis and proliferation were assessed by immunohistochemistry using antibodies to cleaved caspase 3 or Ki67, respectively. The ex vivo tissue explant assay maintained viable tumor cells in an intact tumor microenvironment similar to the in vivo situation over the 120 h culture period. Carboplatin treatment promoted apoptosis in chemosensitive (P = 0.0047) but not chemoresistant cancer tissues. The combination of 4-MU (1 mM) and carboplatin (100 mu M) significantly increased apoptosis (P = 0.0111) and reduced proliferation (P = 0.0064) in chemoresistant tissues. Overall, our results show that the ex vivo explant assay is a robust and cost effective model to assess chemosensitivity and the effect of novel therapeutics in ovarian cancer. (c) 2018 Elsevier B.V. All rights reserved.
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