Combination of IL-24 and cisplatin inhibits angiogenesis and lymphangiogenesis of cervical cancer xenografts in a nude mouse model by inhibiting VEGF, VEGF-C and PDGF-B.

The aim of the present study was to investigate the synergistic inhibitory effects of recombinant IL-24 delivered by pDC316-hIL-24 transfection and cisplatin (DDP) on angiogenesis and lymphangiogenesis in a cervical cancer xenograft model established in nude mice. Thirty-six mice (successful model) were randomly divided into six groups (n=6 in each): i) phosphate-buffered saline control; ii) empty plasmid; iii) half-dose DDP; iv) recombinant interleukin (IL)-24; v) full-dose DDP; and vi) combined treatment. Tumor growth and animal weight were measured every 3 days. Animals were sacrificed by cervical dislocation at 2 weeks after the cessation of treatment. Tumor inhibition was compared after intervention. Lymph node metastasis was evaluated by immunohistochemical (IHC) analysis of vascular endothelial growth factor (VEGF), VEGF-C and VEGFR-3. Platelet-derived growth factor (PDGF)-B expression was also investigated by western blot analysis. Microvessel density was evaluated by IHC analysis of CD34 expression. The tumor growth was slower or reduced in the IL-24 and half-dose DDP+IL-24 groups. The expression of VEGF and microvessel density in the IL-24 group was significantly lower than that in the other groups. VEGF (VEGF-A), VEGF-C, VEGFR-3 and PDGF-B expression was significantly decreased in the IL-24 and half-dose DDP+IL-24 groups compared with that in the other groups (P<0.001). The recombinant plasmid pDC316-hIL-24 acts synergistically with cisplatin to inhibit tumor growth and angiogenesis. Our data indicate that these effects are mediated by downregulation of VEGF, VEGF-C and PDGF-B expression. Thus, IL-24 may enhance tumor chemosensitivity to cisplatin, which may be an important strategy for reducing the side-effects of this chemotherapy.