title: The pigment epithelial-derived factor gene loaded in PLGA nanoparticles for therapy of colon carcinoma.
abstract: Colon carcinoma is one of the common malignant tumors and has high morbidity and mortality in the world. Pigment epithelial-derived factor (PEDF) has been found to be the most potent natural inhibitor of angiogenesis and PEDF gene has been extensively used for the therapy of tumors, which suggests a potential approach to the therapy of colon carcinoma. However, the transfer of PEDF gene largely depends on the effective gene delivery systems. Poly (lactic-co-glycolic acid) nanoparticles (PLGANPs) have been extensively used for gene therapy due to its low-toxicity, biocompatibility and biodegradability, due to its potential to be an excellent carrier of the PEDF gene. We investigated the effect of PEDF gene loaded in PLGA nanoparticles (PEDF-PLGANPs) on the mouse colon carcinoma cells (CT26s) in vitro and in vivo. Blank PLGANPs (bPLGANPs) showed lower cytotoxicity than PEI to the CT26s. In vitro, PEDF-PLGANPs directly induced CT26 apoptosis and inhibit human umbilical vein endothelial cell (HUVEC) proliferation. In vivo, PEDF-PLGANPs inhibited CT26 tumors growth by inducing CT26 apoptosis, decreasing MVD and inhibiting angiogenesis. Our present study demonstrates the inhibitory effect of PEDF-PLGANPs on the growth of CT26s in vitro and in vivo for the first time. PLGANP-mediated PEDF gene could provide an innovative strategy for the therapy of colon carcinoma.
authors.affiliation: School of Life Science, Sichuan University, Chengdu, PR China.
authors.forename: Feng-Yu
authors.initials: FY
authors.lastname: Cui
authors.forename: Xiang-Rong
authors.initials: XR
authors.lastname: Song
authors.forename: Zhi-Yong
authors.initials: ZY
authors.lastname: Li
authors.forename: Shuang-Zhi
authors.initials: SZ
authors.lastname: Li
authors.forename: Bo
authors.initials: B
authors.lastname: Mu
authors.forename: Yong-Qiu
authors.initials: YQ
authors.lastname: Mao
authors.forename: Yu-Quan
authors.initials: YQ
authors.lastname: Wei
authors.forename: Li
authors.initials: L
authors.lastname: Yang
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D002277:Carcinoma / Q000098:blood supply / Q000235:genetics / Q000378:metabolism / Q000473:pathology / Q000628:therapy*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D003110:Colonic Neoplasms / Q000098:blood supply / Q000235:genetics / Q000378:metabolism / Q000473:pathology / Q000628:therapy*; D000229:Dependovirus / Q000235:genetics; D042783:Endothelial Cells / Q000187:drug effects; D005136:Eye Proteins / Q000096:biosynthesis / Q000235:genetics*; D018014:Gene Transfer Techniques; D015316:Genetic Therapy / Q000379:methods*; D005822:Genetic Vectors; D006801:Humans; D019344:Lactic Acid / Q000737:chemistry* / Q000633:toxicity; D051379:Mice; D008807:Mice, Inbred BALB C; D053758:Nanoparticles; D009389:Neovascularization, Pathologic / Q000235:genetics / Q000378:metabolism / Q000517:prevention & control; D009414:Nerve Growth Factors / Q000096:biosynthesis / Q000235:genetics*; D011100:Polyglycolic Acid / Q000737:chemistry* / Q000633:toxicity; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D015843:Serpins / Q000096:biosynthesis / Q000235:genetics*; D013997:Time Factors; D047368:Tumor Burden / Q000187:drug effects; D000099174:Pigment Epithelium-Derived Factor
chemical_list: D005136:Eye Proteins; D019344:Lactic Acid; D009414:Nerve Growth Factors; D011100:Polyglycolic Acid; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D015843:Serpins; D000099174:Pigment Epithelium-Derived Factor