Enhanced antitumor effect of biodegradable cationic heparin-polyethyleneimine nanogels delivering FILIP1L∆C103 gene combined with low-dose cisplatin on ovarian cancer

Abstract

FILIP1LΔC103 (COOH terminal truncation mutant 1-790 of Filamin A Interacting Protein 1-Like) has been identified to hold therapeutic potential for suppressing tumor growth. Cisplatin (DDP) is commonly used as a first-line drug in the treatment for ovarian cancer. The usage of polymeric nanoparticles to deliver functional genes intraperitoneally holds much promise as an effective therapy for ovarian cancer. In this study, a recombinant plasmid expressing FILIP1LΔC103 (FILIP1LΔC103-p) was constructed, and HPEI nanogels were prepared to deliver FILIP1LΔC103-p into SKOV3 cells. The expression of FILIP1LΔC103 in vitro and in vivo was determined using RT-PCR and Western Blotting. Moreover, in vivo treatment experiments were conducted on nude mice bearing SKOV3 ovarian cancer. The mice were treated with 5% glucose, HPEI+E-p, HPEI+FILIP1LΔC103-p, DDP or HPEI+FILIP1LΔC103-p plus DDP, respectively. Tumor weights were evaluated throughout the treatment duration. The cell proliferation and apoptosis were evaluated by Ki-67 immunochemical staining and TUNEL assay respectively, and the anti-angiogenic effect was assessed by CD31 immunochemical staining and alginate-encapsulated tumor cell assay. FILIP1LΔC103-p could be efficiently transfected into SKOV3 cells by HPEI nanogels. The combination of HPEI+FILIP1LΔC103-p with DDP exerted enhanced antitumor activity compared with HPEI+FILIP1LΔC103-p or DDP alone. Significant reduction of tumor cells proliferation, augmentation of tumor cells apoptosis and suppression of angiogenesis were observed in the combination group compared with controls. Our results demonstrated synergistic antineoplastic activity of combined FILIP1LΔC103 and low-dose DDP with no apparent toxicity, indicating a potential application of the combined approach in the treatment of ovarian cancer.