Effect of hydroxyapatite nanoparticles on the growth and p53/c-Myc protein expression of implanted hepatic VX2 tumor in rabbits by intravenous injection.
OBJECTIVE
To evaluate the effect of hydroxyapatite nano-particles (Nano HAP) by intravenous injection on the inhibition of implanted hepatic VX(2) tumor growth in rabbits and cell p53/c-Myc protein expression.


METHODS
60 hepatic VX(2) tumor-bearing rabbits was randomly divided into five groups. Nano HAP collosol 20 mg/kg, 40 mg/kg, 5-FU solutions 20 mg/mL, mixed liquor of 5-FU solution 20 mg/mL and Nano HAP collosol 20 mg/kg were infused by vein, normal saline conducted as the control. The general state, weight, liver function and gross tumor volume were detected dynamically. The expression of p53 and c-Myc gene protein in tumor tissue was detected by immunohistochemistry methods.


RESULTS
The growth of implanted hepatic VX(2) tumors was significantly inhibited in all therapy groups, 3 wk after the injection, the tumor control rates in Nano HAP collosol groups were 25.5% and 32.5% respectively, and the gross tumor volumes were obviously less than that of control group. (24.81 +/- 5.17 and 22.73 +/- 4.23 vs 33.32 +/- 5.26, P<0.05). The tumor control rate of 5-FU group was 43.7% (18.74 +/- 4.40 vs 33.32 +/- 5.26, P<0.05), but the general state of the animals after injection aggravated; and the adverse reaction in the drug combination group obviously decreased. Due to the effect of Nano HAP, the positive expression of tumor associated the mutated p53 and c-Myc in tumor tissue was decreased obviously compared with the control group.


CONCLUSIONS
Nano HAP has evident inhibitory action on rabbit implanted hepatic VX(2) tumor in vivo, which may be the result of decreasing the expression of the mutated p53 and c-myc, and drug combination can obviously decrease the adverse reaction of 5-FU.
Hu
Jun
J
Department of General Surgery, Zhongnan Hospital, Wuhan University, Wuhan 430071, Hubei Province, China.
Liu
Zhi-Su
ZS
Tang
Sheng-Li
SL
He
Yue-Ming
YM
D000818:Animals; D000964:Antimetabolites, Antineoplastic / Q000009:adverse effects / Q000627:therapeutic use; D001672:Biocompatible Materials / Q000008:administration & dosage / Q000494:pharmacology*; D049109:Cell Proliferation / Q000187:drug effects*; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D004195:Disease Models, Animal; D004359:Drug Therapy, Combination; D017886:Durapatite / Q000008:administration & dosage / Q000494:pharmacology*; D005260:Female; D005472:Fluorouracil / Q000009:adverse effects / Q000627:therapeutic use; D015972:Gene Expression Regulation, Neoplastic; D007275:Injections, Intravenous; D008099:Liver / Q000473:pathology / Q000503:physiopathology; D008113:Liver Neoplasms / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology*; D008297:Male; D053758:Nanoparticles / Q000008:administration & dosage; D011817:Rabbits; D011897:Random Allocation; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism*
D000964:Antimetabolites, Antineoplastic; D001672:Biocompatible Materials; D004268:DNA-Binding Proteins; C116115:MYCBP protein, human; D014157:Transcription Factors; D016159:Tumor Suppressor Protein p53; D017886:Durapatite; D005472:Fluorouracil