The pigment epithelial-derived factor gene loaded in PLGA nanoparticles for therapy of colon carcinoma.
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.
Cui
Feng-Yu
FY
School of Life Science, Sichuan University, Chengdu, PR China.
Song
Xiang-Rong
XR
Li
Zhi-Yong
ZY
Li
Shuang-Zhi
SZ
Mu
Bo
B
Mao
Yong-Qiu
YQ
Wei
Yu-Quan
YQ
Yang
Li
L
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
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