The experimental study of wild-type p53 and double suicide gene for interventional therapy in liver carcinoma
DU Tong, NIU Hong-xin, ZHANG Xi-kun, WANG Ruo-gu
Published 2013-08-28
Cite as Chin J Hepatobiliary Surg, 2013,19(08): 606-610. DOI: 10.3760/cma.j.issn.1007-8118.2013.08.014
Abstract
Objective To investigate interventional procedures and polygene feasibility for the treatment of liver carcinoma.Methods pCMV-p53 plasmid-liposome complex and concentrated TKCD retrovirus of supernatant liquid were prepared along with rabbit VX2 liver tumor models of 50 adult New Zealand rabbits.VX2 liver tumors about 2 cm in diameter from 45 adult rabbits were randomly divided into 5 groups of 9.Group 1 was the control group that used 0.9% sodium chloride as a placebo.Group 2 had transcatheter arterial embolization with lipiodol as treatment.Group 3 was the lipiodol and p53 group.Group 4 was the lipiodol and TK/CD group.Group 5 was the lipiodol,p53,and TK/CD group.The microtubule(1.2f)was inserted from the femoral to hepatic artery,tumor supply arteries were demonstrated by angiograms,and the drug was slowly injected under x-ray.The VX2 liver tumors were examined with B-ultrasound and computed tomography for maximum diameter (a) and minimum diameter (b) before and 10 days after interventional therapy.Gross tumor volume (V=ab2/2) and tumor growth rate were calculated.All the adult rabbits were euthanized 8 weeks after interventional therapy (including natural deaths).Histopathological examination was taken and survival time was observed.Results The tumor volume among the 5 groups had no significant difference before interventional therapy (P>0.05).Ten days after interventional therapy,analysis of the tumor volume for variance and the T-test were carried out.The results showed that each group compared to the control showed a significant difference in inhibiting cancer growth (P<0.05).The lipiodol,p53,and TK/CD group showed the best effect.According to factorial statistic analysis (2x2),p53 or TK/CD combined with lipiodol therapy can control the tumor obviously,but no mutual synergism effect was found (P=0.793).Each treatment group showed a significant difference of prolonged survival time compared to the control group (P<0.01).The multi-treatment or multi-gene group showed the best curative effects.Conclusions Interventional therapy can be the ideal path for administering medications for gene therapy.Transcatheter arterial embolization with lipiodol,wild-type p53 gene,TK/GCV,and CD/5-Fc applied in combination can control tumor growth and prolong survival time.
Key words:
Hepatoma; Interventional therapy; Gene therapy
Contributor Information
DU Tong
Department of General Surgery, Affiliated Hospital of Shandong Academy of Medical Science, Jinan 250031, China
NIU Hong-xin
Department of General Surgery, Affiliated Hospital of Shandong Academy of Medical Science, Jinan 250031, China
ZHANG Xi-kun
Department of General Surgery, Affiliated Hospital of Shandong Academy of Medical Science, Jinan 250031, China
WANG Ruo-gu
Department of General Surgery, Affiliated Hospital of Shandong Academy of Medical Science, Jinan 250031, China