In vivo antitumor activity of liposome-plasmid DNA encoding mutant survivin-T34A in cervical cancer

The aim of the present study was to investigate the influence of liposome-plasmid encoding mutant survivin-T34A (PST34A) on tumor growth in cervical cancer in vivo. Liposome-plasmid DNA encoding mutant survivin-T34A was constructed and administered via an intraperitoneal injection in mice inoculated with cervical cancer cells. Following the establishment of the tumor model, the animals were randomly divided into four groups: i) The normal saline group (NS; 100 µl sterile saline once/3 days for 15 days); ii) the 1,2-dioleoyl-3-trimethylammonium-propane (DOTAP) control (100 µg DOTAP once/3 days for 15 days); iii) the plasmid PST34A (10 µg PST34A once/3 days for 15 days); and iv) the PST34A+DOTAP (10 µg PST34A+100 µg DOTAP once/3 days for 15 days). All treatments were administered via intraperitoneal injections. Tumor growth was evaluated following injection with liposome-plasmid DNA encoding mutant survivin-T34A. Apoptosis of cells in ascitic fluid was detected by flow cytometry. The expression of Ki67 and CD34 was detected by immunohistochemical staining. Administration of liposome-plasmid complexes encoding mutant survivin-T34A inhibited tumor growth, reduced the number of tumor nodules and the volume of ascitic fluid, and decreased abdomen circumference and tumor weight. The number of Ki67-positive cells was markedly reduced in the DOTAP+PST34A group compared with the remaining groups. Flow cytometry demonstrated that the number of cells in the sub-G1 phase (apoptosis) increased in the DOTAP+PST34A group compared with all other groups. In addition, tumors in the DOTAP+PST34A group exhibited lower microvessel density compared with all other groups. In the present study, liposome-plasmid DNA encoding mutant survivin-T34A could inhibit tumor growth of cervical cancer. This inhibition may be associated with an increase in the apoptosis rate of tumor cells and a reduction in angiogenesis.