Trans-arterial gene therapy for hepatocellular carcinoma in a rabbit model.
OBJECTIVE
To study the effect of adenovirus (Ad)-p53 gene therapy on hepatocellular carcinoma (HCC) in a rabbit model.


METHODS
VX2 tumor was grown in the liver of 24 rabbits. Animals were divided into four groups: group A receiving trans-arterial gene therapy (Ad-p53) only, group B receiving combined Ad-p53 therapy and trans-arterial embolization (lipiodol), group C receiving trans-arterial chemoembolization (lipiodol + mitomycin C), control group (D) receiving sodium chloride. Tumor volume (V1) was measured by using MRI (d 13). Interventional procedure was applied (d 14). Tumor volume (V2) was assessed by MRI (d 21) and the mean ratio (V2/V1) was calculated. After the second MRI, specimens of the liver were abstained and examined immunohistochemically using mutant-type p53 antibody. The positive expression was scored.


RESULTS
Compared with control group (chi= 3.14 +/- 0.64), therapeutic groups all showed a significant decrease in the tumor growth ratio (P<0.05). A slight difference was found between group A (chi = 2.35 +/- 0.59) and group B (chi = 1.75 +/- 0.28) (P=0.048). No statistically significant difference was observed between group B and group C (chi = 2.00 +/- 0.44). The positive expression rate of mutant-type p53 was the lowest in group B and significantly different between group A and group C (P<0.05). Compared to the control subjects, groups A and C both showed a decrease in the expression of mutant-type p53, but there was no significant difference between them.


CONCLUSIONS
Trans-arterial Ad-p53 gene therapy can reduce tumor growth of HCC in rabbit model.
Gu
Tao
T
Department of Radiology, Qilu Hospital of Shandong University, 107 Wenhuaxi Road, Jinan 250012, Shandong Province, China.
Li
Cai-Xia
CX
Feng
Yan
Y
Wang
Qian
Q
Li
Chun-Hai
CH
Li
Chuan-Fu
CF
D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000627:therapeutic use; D006528:Carcinoma, Hepatocellular / Q000235:genetics / Q000473:pathology / Q000628:therapy*; D003131:Combined Modality Therapy; D004195:Disease Models, Animal; D004621:Embolization, Therapeutic / Q000379:methods*; D015972:Gene Expression Regulation, Neoplastic; D016158:Genes, p53; D015316:Genetic Therapy / Q000379:methods*; D007459:Iodized Oil; D008113:Liver Neoplasms / Q000235:genetics / Q000473:pathology / Q000628:therapy*; D008279:Magnetic Resonance Imaging; D016685:Mitomycin / Q000627:therapeutic use; D011817:Rabbits; D047368:Tumor Burden; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism
D000903:Antibiotics, Antineoplastic; D016159:Tumor Suppressor Protein p53; D016685:Mitomycin; D007459:Iodized Oil