Ovarian cancer is the most lethal of all gynaecological cancers, mostly because it is detected at late clinical stages, when the treatment is less effective [
1]. Late stage ovarian cancer presents with widespread peritoneal dissemination and ascites. Treatment usually involves aggressive cytoreductive surgery, and modern combination chemotherapy (platinum and paclitaxel) or i.p. cisplatin based-chemotherapy [
2‐
6]. Lack of an adequate screening test for early disease detection and the rapid progression to chemoresistance have prevented appreciable improvement in the five year survival rate of patients with ovarian cancer [
7]. Dissemination of single tumour cells into the peritoneal cavity is the major cause of tumour recurrence even after complete resection of the primary solid tumour [
8,
9]. Currently, there is no effective treatment for peritoneal carcinomatosis [
10]. Preclinical models that mimic the complexity of tumour behaviour and microenvironment in patients are essential for the evaluation of novel chemotherapeutics. These preclinical models include models of spontaneous ovarian carcinoma in experimental animals [
11,
12] or genetically modified animals [
13,
14]. However, the long latency to tumourigenesis and the heterogeneity in the timing of advanced tumour development makes the use of these models in preclinical studies challenging. Ovarian cancer cell lines derived from ascites or primary ovarian tumours have been used extensively and can be very effective for studying the processes controlling growth regulation and chemosensitivity [
15]. However, most of these studies rely on subcutaneous xenografts, that do not provide the relevant tumour microenvironment which that might influence treatment response [
9]. Tumour formation resulting from peritoneal implantation of human ovarian carcinoma cells holds promise as pre-clinical models of human ovarian cancer, as they are relatively rapid to generate and develop in the relevant microenvironment. Expression of Rab25, a member of the Ras superfamily of GTPases, in the ovarian cancer cell line A2780, allows these cells to invade and grow in the peritoneum of mice, resulting in tumour growth accumulation and death recapitulating the peritoneal disseminated disease in humans [
16]. Rab25 was discovered to be the driving event of the 1q22 genomic amplification associated with poor disease-free survival rate following surgical and chemotherapy procedures [
16]. Its enforced expression in ovarian and breast cancer cell lines induced cell number through reduced apoptosis after multiple stress conditions, including UV radiation and exposure to paclitaxel [
16]. These results suggest that Rab25 expression might also influence cisplatin resistance.
In the present study, we have developed a model of peritoneal ovarian carcinomatosis in athymic immunodeficient mice using the A2780 cell line overexpressing Rab25 that can be monitored longitudinally through by bioluminescence. We show that Rab25 expression in this cell line induces cisplatin resistance in vitro and in vivo, although the in vivo resistance to treatment is also determined by the localisation of the tumour. In addition, we confirm increased anti-tumour activity of the novel cisplatin delivery system Cucurbit[7]uril (cisplatin@CB[7]) compared to free cisplatin in the i.p. model which exceeded that observed in the s.c. model. Cucurbit[n]uril is a barrel-shaped molecule, containing a hydrophobic cavity, formed by the acid catalysed condensation of glycoluril and formaldehyde. Cucurbit[n]urils can be synthesised in a variety of sizes (n=5, 6, 7, 8 and 10), and are capable of encapsulating smaller molecules within their cavities. Our results demonstrate that cisplatin@CB [7] may have utility in the treatment of drug-resistant ovarian human cancers and warrant further investigation.