The use of folate-PEG-grafted-hybranched-PEI nonviral vector for the inhibition of glioma growth in the rat.
Combined treatment using nonviral agent-mediated enzyme/prodrug therapy and immunotherapy had been proposed as a powerful alternative method of cancer therapy. The present study was aimed to evaluate the cytotoxicity in vitro and the therapeutic efficacy in vivo when the cytosine deaminase/5-fluorocytosine (CD/5-FC) and TNF-related apoptosis-inducing ligand (TRAIL) genes were jointly used against rat C6 glioma cells. The potency of the FA-PEG-PEI used as a nonviral vector was tested in the FR-expressed C6 glioma cells and Wistar rats. The C6 glioma cells and animal model were treated by the combined application of FA-PEG-PEI/pCD/5-FC and FA-PEG-PEI/pTRAIL. The antitumor effect was evaluated by survival assays and tumor volume. This study revealed a significant increase of cytotoxicity in vitro following the combined application of FA-PEG-PEI/pCD/5-FC and FA-PEG-PEI/pTRAIL treatments in C6 glioma cells. Animal studies showed a significant growth inhibition of the C6 glioma xenografts using the combined treatment. These results demonstrated that the combined treatment generated additive cytotoxic effect in C6 glioma cells in both in vitro and in vivo conditions, and indicated that such treatment method using both enzyme/prodrug therapy and TRAIL immunotherapy might be a promising therapeutic strategy in treating glioma.
Department of Neurology, The Second Affiliated Hospital, Sun Yat-sen University, No. 107 West Road of Riverside, Guangzhou 510120, China.
Bing
B
Liang
Ming-Liang
ML
He
Chu-yan
CY
Chan
Yang-chao
YC
Chen
Xiang-Ping
XP
Li
Yi
Y
Li
Dexian
D
Zheng
Marie C
MC
Lin
Hsiang-Fu
HF
Kung
Xin-Tao
XT
Shuai
Ying
Y
Peng
D000818:Animals; D001932:Brain Neoplasms / Q000628:therapy; D045744:Cell Line, Tumor; D043525:Cytosine Deaminase / Q000235:genetics / Q000502:physiology; D005492:Folic Acid / Q000737:chemistry*; D015316:Genetic Therapy / Q000379:methods*; D005822:Genetic Vectors / Q000737:chemistry*; D005910:Glioma / Q000628:therapy*; D007150:Immunohistochemistry; D008297:Male; D011092:Polyethylene Glycols / Q000737:chemistry*; D011094:Polyethyleneimine / Q000737:chemistry*; D051381:Rats; D017208:Rats, Wistar; D053221:TNF-Related Apoptosis-Inducing Ligand / Q000235:genetics / Q000502:physiology
D053221:TNF-Related Apoptosis-Inducing Ligand; D011092:Polyethylene Glycols; D011094:Polyethyleneimine; D005492:Folic Acid; D043525:Cytosine Deaminase