Hepatic artery infusion of antisense oligodeoxynucleotide and lipiodol mixture transfect liver cancer in rats.
OBJECTIVE
To study the distribution and stability of antisense oligodeoxynucleotide (ASODN) in Walker-256 cells and their distribution in liver, lung and kidney tissues after being infused alone or mixed with lipiodol via hepatic artery in a rat liver tumor model.


METHODS
5'-Isothiocyanate (FITC)-labeled vascular endothelial growth factor (VEGF) ASODN was added into Walker-256 cell culture media. Its distribution in cells was observed by fluorescence microscope at different time points. Walker-256 carcinosarcoma was transplanted into Wistar rat liver to establish a liver cancer model. 5'-FITC-labeled VEGF ASODN mixed with (mixed group, n = 6) or without (TAI group, n = 6) ultra-fluid lipiodol was administrated via hepatic artery. Frozen samples of liver, lung and kidney tissue were taken from rats after 1, 3 and 6 d, respectively. The distribution of ASODN was observed under fluorescent microscope.


RESULTS
ASODN could enter cytoplasm within 2 h and nuclei within 6 h. Accumulation of ASODN reached the peak point in nuclei at 12 h, and then disappeared gradually. No fluorescence could be seen in cells at 48 h. In vivo experiment, on d 1 and 3 the fluorescence staining in liver was stronger in mixed group than in TAI group and more fluorescence could be detected in lung and kidney in TAI group than in mixed group. On d 6, no fluorescence could be detected in TAI group, but faint fluorescence could be seen in mixed group. ASODN could be seen in cancer cells and normal hepatic cells. In mixed group, ASODN was mainly distributed in liver tumor tissues.


CONCLUSIONS
ASODN can transfect Walker-256 cells. ASODN mixed with lipiodol infusion via hepatic artery can be used in the treatment of HCC.
Wu
Han-Ping
HP
Department of Interventional Radiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, Hubei Province, China. shhwhp@public.wh.hb.cn
Feng
Gan-Sheng
GS
Tian
Yuan
Y
D000818:Animals; D002279:Carcinoma 256, Walker / Q000188:drug therapy*; D045744:Cell Line, Tumor; D003287:Contrast Media / Q000493:pharmacokinetics*; D004195:Disease Models, Animal; D016650:Fluorescein-5-isothiocyanate / Q000493:pharmacokinetics; D005456:Fluorescent Dyes / Q000493:pharmacokinetics; D006499:Hepatic Artery; D007459:Iodized Oil / Q000493:pharmacokinetics*; D008113:Liver Neoplasms / Q000188:drug therapy*; D008297:Male; D009368:Neoplasm Transplantation; D020319:Oligodeoxyribonucleotides, Antisense / Q000493:pharmacokinetics*; D051381:Rats; D017208:Rats, Wistar; D013047:Specific Pathogen-Free Organisms; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics
D003287:Contrast Media; D005456:Fluorescent Dyes; D020319:Oligodeoxyribonucleotides, Antisense; D042461:Vascular Endothelial Growth Factor A; D007459:Iodized Oil; D016650:Fluorescein-5-isothiocyanate