Efficacy assessment of sustained intraperitoneal paclitaxel therapy in a murine model of ovarian cancer using bioluminescent imaging.
We evaluated the pre-clinical efficacy of a novel intraperitoneal (i.p.) sustained-release paclitaxel formulation (PTX(ePC)) using bioluminescent imaging (BLI) in the treatment of ovarian cancer. Human ovarian carcinoma cells stably expressing the firefly luciferase gene (SKOV3(Luc)) were injected i.p. into SCID mice. Tumour growth was evaluated during sustained or intermittent courses of i.p. treatment with paclitaxel (PTX). In vitro bioluminescence strongly correlated with cell survival and cytotoxicity. Bioluminescent imaging detected tumours before their macroscopic appearance and strongly correlated with tumour weight and survival. As compared with intermittent therapy with Taxol, sustained PTX(ePC) therapy resulted in significant reduction of tumour proliferation, weight and BLI signal intensity, enhanced apoptosis and increased survival times. Our results demonstrate that BLI is a useful tool in the pre-clinical evaluation of therapeutic interventions for ovarian cancer. Moreover, these results provide evidence of enhanced therapeutic efficacy with the sustained PTX(ePC) implant system, which could potentially translate into successful clinical outcomes.
Vassileva
V
V
Department of Pharmaceutical Sciences, Leslie Dan Faculty of Pharmacy, University of Toronto, 144 College Street, Rm. 1003, Toronto, Ontario, Canada M5S 3M2.
Moriyama
E H
EH
De Souza
R
R
Grant
J
J
Allen
C J
CJ
Wilson
B C
BC
Piquette-Miller
M
M
D000818:Animals; D001835:Body Weight; D045744:Cell Line, Tumor; D002470:Cell Survival; D004195:Disease Models, Animal; D018450:Disease Progression; D005260:Female; D006801:Humans; D007274:Injections, Intraperitoneal; D008163:Luminescent Measurements; D051379:Mice; D016513:Mice, SCID; D010051:Ovarian Neoplasms / Q000188:drug therapy* / Q000473:pathology*; D017239:Paclitaxel / Q000008:administration & dosage* / Q000627:therapeutic use*; D015996:Survival Rate; D023041:Xenograft Model Antitumor Assays
D017239:Paclitaxel