Liposomal plasmid DNA encoding human thymosin alpha and interferon omega potently inhibits liver tumor growth in ICR mice.
OBJECTIVE
To evaluate the potential therapeutic effect of liposomal gene delivery, genes encoding for human thymosin alpha1 (Talpha1) and interferon omega1 were injected via the tail vein into mice bearing a Hep-A-22 liver tumor.


METHODS
The cDNA of human Talpha1 and interferon omega1 were obtained by synthesis or reverse transcription-polymerase chain reaction (RT-PCR), respectively. Eukaryotic expressing vectors pIRES2, encoding Talpha1 and/or interferon omega1, were constructed and injected with liposome via the tail vein into ICR mice bearing a Hep-A-22 tumor. The potency of tumor inhibition was evaluated when three treated groups were compared with the group receiving the empty vector. Apoptosis of tumor cells was investigated by analyzing DNA fragmentation.


RESULTS
Only the group treated with dual-gene plasmid reached an eligible level of tumor inhibition (43%). The difference in tumor weight was statistically significant between the Talpha1 gene or the interferon omega1 gene treated groups and the control (P<0.05), and highly significant between the dual-gene treated group and the control (P<0.01). DNA ladder was observed in the tumor cells from the purpose gene treated groups but not from the control.


CONCLUSIONS
The dual-gene plasmid-liposome complex showed more potent inhibition than the single gene constructs on the growth of Hep-A-22 tumor cells in mice, which may be attributed to indirect and additive induction of apoptosis in tumor cells by increased expression of Talpha1 and interferon omega1.
Chen
Pei Fu
PF
Medical School, Nanjing University, Nanjing, Jiangsu Province, China.
Fu
Geng Feng
GF
Zhang
Hong Ying
HY
Xu
Gen Xing
GX
Hou
Ya Yi
YY
D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage*; D017209:Apoptosis / Q000187:drug effects; D004269:DNA, Bacterial / Q000235:genetics*; D018450:Disease Progression; D005260:Female; D006801:Humans; D007370:Interferon Type I / Q000008:administration & dosage*; D008081:Liposomes; D008114:Liver Neoplasms, Experimental / Q000188:drug therapy* / Q000473:pathology; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D010957:Plasmids / Q000235:genetics*; D000077596:Thymalfasin; D013947:Thymosin / Q000008:administration & dosage / Q000031:analogs & derivatives*; D016896:Treatment Outcome
D000970:Antineoplastic Agents; D004269:DNA, Bacterial; D007370:Interferon Type I; D008081:Liposomes; C063743:interferon omega 1; D013947:Thymosin; D000077596:Thymalfasin