Claudin-3 (CLDN3) is a
tight junction protein that is overexpressed in 90% of ovarian
tumors. Previous in vitro studies have indicated that CLDN3 overexpression promotes the migration, invasion, and survival of
ovarian cancer cells. Here, we investigated the efficacy of lipidoid-formulated CLDN3
siRNA in 3 different
ovarian cancer models. Intratumoral injection of lipidoid/CLDN3
siRNA into OVCAR-3 xenografts resulted in dramatic silencing of CLDN3, significant reduction in cell proliferation, reduction in
tumor growth, and a significant increase in the number of apoptotic cells.
Intraperitoneal injection of lipidoid-formulated CLDN3
siRNA resulted in a substantial reduction in
tumor burden in MISIIR/TAg transgenic mice and mice bearing
tumors derived from mouse ovarian surface epithelial cells.
Ascites development was reduced in CLDN3
siRNA-treated mice, suggesting the treatment effectively suppressed
metastasis. Toxicity was not observed after multiple i.p.
injections. Importantly, treatment of mice with nonimmunostimulatory 2'-OMe modified CLDN3
siRNA was as effective in suppressing
tumor growth as unmodifed
siRNA. These results suggest that lipidoid-formulated CLDN3
siRNA has potential as a therapeutic for
ovarian cancer.