[The effects of lipiodol-hydroxyapatite nanoparticle on apoptosis, proliferation, and angiogenesis in hepatic tumor: experiment with rabbits].
OBJECTIVE
To investigate the effects of lipiodol-hydroxyapatite nanoparticle (lipi-nHAP) on the growth, necrosis, apoptosis, proliferation, and angiogenesis of hepatic tumor.


METHODS
Ultrasound-emulsification was used to make lipi-nHAP Eighty New Zealand white rabbits underwent implantation of carcinoma cells of the line VX2 into the left lobe of liver. Two weeks later the rabbits underwent catheterization into the gastroduodenal artery so that, and then the rabbits were randomly divided into four equal groups to receive infusion via the hepatic artery of different drugs: physiological saline (Group A), lipiodol (Group B), adriamycin + lipiodol (Group C), and lipi-nHAP (Group D). Seven and 14 days after the treatment the size of tumor was observed by spiral CT scan, and the volume and growth rate of tumor were calculated. Two weeks after the treatment 8 rabbits from each group were killed and their liver tumors were taken out and the survival rates of remaining rabbits were observed. The necrosis rate of the liver tumor was assessed by measuring the area of the tumor and the necrosis. The apoptotic rate was examined by TUNEL method. Mcrovessel density (MVD) was examined by immunohistochemistry anti-CD31 antibody. Anti-proliferating cell nuclear antigen (PCNA) monoclonal antibody was used to detect the expression of PCNA so as to calculate the proliferation index of the cells.


RESULTS
The tumor volume and growth rate of Group D 7 and 14 days after treatment were both significantly lower than those of other groups (all P < 0.05) and the necrosis rate and apoptotic index of Group D were both significantly higher than those of other groups (all P < 0.05). The values of MVD were higher in Groups C and D compared with those of Group A. Compared with those in other groups, the values of MVD and expression level of PCNA were significantly lower in group D (all P < 0.05). The survival time of Group D was longer than those of other groups (all P < 0.05).


CONCLUSIONS
lipi-nHAP can suppress the growth of tumor, increase the tumor's necrosis rate and apoptotic index, inhibit the development of neovascularization, decrease the expression level of PCNA of residual tumor, and prolong the surviving time of the animals with hepatic tumor. It may become an effective embolization material to treat liver cancer.
Sun
Zhen-Gang
ZG
Hepatic Surgery Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China. sunzhengang1968@yahoo.com.cn
Chen
Xiao-Ping
XP
Huang
Zhi-Yong
ZY
Yang
Guo-Hua
GH
Guan
Jian
J
Hu
Dao-Yu
DY
Mu
La-de
LD
Xia
Xi-Gang
XG
Li
Gao-Peng
GP
Zhang
Wan-Guang
WG
Li
Zhen
Z
D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D049109:Cell Proliferation / Q000187:drug effects*; D017886:Durapatite / Q000008:administration & dosage / Q000627:therapeutic use*; D005260:Female; D007150:Immunohistochemistry; D020287:In Situ Nick-End Labeling; D007459:Iodized Oil / Q000008:administration & dosage / Q000627:therapeutic use*; D008099:Liver / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D008114:Liver Neoplasms, Experimental / Q000098:blood supply / Q000188:drug therapy* / Q000473:pathology; D008297:Male; D053758:Nanoparticles / Q000008:administration & dosage / Q000627:therapeutic use; D009366:Neoplasm Seeding; D009389:Neovascularization, Pathologic / Q000473:pathology / Q000517:prevention & control*; D019408:Platelet Endothelial Cell Adhesion Molecule-1 / Q000032:analysis; D018809:Proliferating Cell Nuclear Antigen / Q000032:analysis / Q000096:biosynthesis; D011817:Rabbits; D011897:Random Allocation; D016896:Treatment Outcome; D047368:Tumor Burden / Q000187:drug effects
D019408:Platelet Endothelial Cell Adhesion Molecule-1; D018809:Proliferating Cell Nuclear Antigen; D007459:Iodized Oil; D017886:Durapatite