Inhibition of choriocarcinoma by Fe3O4-dextran-anti-ß-human chorionic gonadotropin nanoparticles containing antisense oligodeoxynucleotide of heparanase

Abstract

Liu Huining,1 Zhang Yi,1 Tang Dihong,2 Pan Yifeng,3 Xia Man,2 Yang Ting,2 Cai Jingting1,2 1Department of Obstetrics and Gynecology, Xiangya Hospital, 2Department of Gynecological Oncology, Hunan Provincial Tumor Hospital, 3National Hepatobiliary and Enteric Surgery Research Center, Central South University, Changsha, Hunan, People's Republic of China Objective: To observe the influence of Fe3O4-dextran-anti-ß-human chorionic gonadotropin (HCG) carrying heparanase (Hpa) antisense oligodeoxynucleotide (ASODN), via the invasion, proliferation, and Hpa expression of JEG-3 cell lines and inhibitory effect of transplanted choriocarcinoma tumor growth. Methods: The different abilities of invasion and proliferation between transfected JEG-3 and untransfected JEG-3 were measured by Matrigel invasion assay and 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay in vitro. The effect of Hpa ASODN transfection on the expression of Hpa mRNA and protein was measured by reverse-transcription polymerase chain reaction and Western blot. The transplanted choriocarcinoma tumors were taken out to calculate the inhibitory effect on tumor growth of Hpa ASODN. Results: In this study, we found that: (1) the invasive ability of JEG-3 cells was inhibited sufficiently (P < 0.05) after JEG-3 cells were transfected by Fe3O4-dextran-anti-βHCG carrying Hpa ASODN; (2) after JEG-3 cells were transfected by Fe3O4-dextran-anti-βHCG carrying Hpa ASODN at 48 and 72 hours, the proliferative ability of JEG-3 cells was inhibited sufficiently (P < 0.05); (3) the expression of Hpa mRNA and protein in JEG-3 cells was inhibited efficiently after JEG-3 cells were transfected by Fe3O4-dextran-anti-βHCG carrying Hpa ASODN (P < 0.05); and (4) Fe3O4-dextran-anti-βHCG carrying Hpa ASODN had an inhibitory effect on the transplanted choriocarcinoma tumor growth (P < 0.05) and was harmless on nude mice. Conclusion: Fe3O4-dextran-anti-βHCG carrying Hpa ASODN weakened the invasive and proliferative ability of choriocarcinoma, with a significant inhibitory effect on the transplanted choriocarcinoma tumor. Therefore, Fe3O4-dextran-anti-βHCG carrying Hpa ASODN is an effective gene therapy, and Fe3O4-dextran-anti-βHCG nanoparticles are a harmless and effective gene vector. Keywords: heparanase, antisense oligodeoxynucleotide, Fe3O4-dextran-anti-βHCG nanoparticles, choriocarcinoma, invasive ability