title: 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.
abstract: 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.
authors.affiliation: The First Hospital of Shanxi Medical University, Taiyuan, Shanxi, P.R. China.
authors.forename: Zhaoxia
authors.initials: Z
authors.lastname: Wang
authors.affiliation: The First Hospital of Shanxi Medical University, Taiyuan, Shanxi, P.R. China.
authors.forename: Jiyuan
authors.initials: J
authors.lastname: Lv
authors.affiliation: Linfen City People's Hospital, Linfen, Shanxi, P.R. China.
authors.forename: Tiantian
authors.initials: T
authors.lastname: Zhang
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D002945:Cisplatin / Q000378:metabolism*; D004195:Disease Models, Animal; D005260:Female; D006367:HeLa Cells; D006801:Humans; D007378:Interleukins / Q000378:metabolism*; D042583:Lymphangiogenesis / Q000502:physiology*; D008207:Lymphatic Metastasis / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D055806:Microvessels / Q000378:metabolism / Q000473:pathology; D009389:Neovascularization, Pathologic / Q000378:metabolism / Q000473:pathology*; D020574:Proto-Oncogene Proteins c-sis / Q000378:metabolism*; D002583:Uterine Cervical Neoplasms / Q000378:metabolism / Q000473:pathology*; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism*; D042582:Vascular Endothelial Growth Factor C / Q000378:metabolism*; D023041:Xenograft Model Antitumor Assays / Q000379:methods; D000099180:Interleukin-24
chemical_list: D002945:Cisplatin; D007378:Interleukins; D020574:Proto-Oncogene Proteins c-sis; D042461:Vascular Endothelial Growth Factor A; D042582:Vascular Endothelial Growth Factor C; D000099180:Interleukin-24; C467484:VEGFA protein, human