Cisplatin is normally administered in
chemotherapy for
ovarian cancer, but is accompanied by severe dose-dependent toxicity. The combination of
cisplatin with other
antitumor agents may be a useful alternative for achieving higher antitumor efficiency and lower toxicity.
Claudin-3 (CLDN3), a commonly upregulated gene in 90% of
ovarian cancers, has been identified as a novel therapeutic target of
ovarian cancer. Therefore, in the present study, we constructed a recombinant plasmid carrying an
shRNA targeting CLDN3 (pshCLDN3), and investigated the antitumor effects of the combination
therapy of pshCLDN3 and a low-dose of
cisplatin for the treatment of
ovarian cancer.
Heparin-
polyethyleneimine (HPEI)
nanogel, a novel gene carrier with superior biodegradability, excellent blood compatibility and low-toxicity, was used to deliver pshCLDN3 into
ovarian cancer cells. The knockdown efficiency was determined by western blot analysis and CLDN3 immunostaining. Nude mice bearing intraperitoneal ovarian
carcinomas were treated with pshCLDN3/HPEI complexes, low-dose
cisplatin, pshCLDN3/HPEI plus low-dose
cisplatin or control agents, respectively. The results showed that pshCLDN3/HPEI effectively suppressed the expression of CLDN3 in
ovarian cancer. The combination
therapy of pshCLDN3/HPEI and low-dose
cisplatin exhibited enhanced antitumor activity, when compared with either agent alone, as evidenced by mean
tumor weight analysis, Ki-67 immunostaining analysis and TUNEL assay, without obvious systemic toxicity. These results indicate that pshCLDN3/HPEI combined with low-dose
cisplatin demonstrates apparent synergistic antitumor activity without marked toxicity. Our study offers a novel therapeutic strategy for the treatment of
ovarian cancer.