Magnetite nanoparticles inhibit tumor growth and upregulate the expression of p53/p16 in Ehrlich solid carcinoma bearing mice.
BACKGROUND
Magnetite nanoparticles (MNPs) have been widely used as contrast agents and have promising approaches in cancer treatment. In the present study we used Ehrlich solid carcinoma (ESC) bearing mice as a model to investigate MNPs antitumor activity, their effect on expression of p53 and p16 genes as an indicator for apoptotic induction in tumor tissues.


METHODS
MNPs coated with ascorbic acid (size: 25.0±5.0 nm) were synthesized by co-precipitation method and characterized. Ehrlich mice model were treated with MNPs using 60 mg/Kg day by day for 14 injections; intratumorally (IT) or intraperitoneally (IP). Tumor size, pathological changes and iron content in tumor and normal muscle tissues were assessed. We also assessed changes in expression levels of p53 and p16 genes in addition to p53 protein level by immunohistochemistry.


RESULTS
Our results revealed that tumor growth was significantly reduced by IT and IP MNPs injection compared to untreated tumor. A significant increase in p53 and p16 mRNA expression was detected in Ehrlich solid tumors of IT and IP treated groups compared to untreated Ehrlich solid tumor. This increase was accompanied with increase in p53 protein expression. It is worth mentioning that no significant difference in expression of p53 and p16 could be detected between IT ESC and control group.


CONCLUSIONS
MNPs might be more effective in breast cancer treatment if injected intratumorally to be directed to the tumor tissues.
Department of Zoology, Faculty of Science, Cairo University, Giza, Egypt.
Heba
H
Bassiony
Department of Zoology, Faculty of Science, Cairo University, Giza, Egypt.
Salwa
S
Sabet
Nanotechnology & Advanced Materials Central Lab, Agriculture Research Center, Giza, Egypt.
Taher A
TA
Salah El-Din
Department of Zoology, Faculty of Science, Cairo University, Giza, Egypt.
Mona M
MM
Mohamed
Department of Zoology, Faculty of Science, Cairo University, Giza, Egypt.
Akmal A
AA
El-Ghor
D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000494:pharmacology; D001205:Ascorbic Acid / Q000008:administration & dosage* / Q000494:pharmacology; D002286:Carcinoma, Ehrlich Tumor / Q000188:drug therapy* / Q000378:metabolism; D019941:Cyclin-Dependent Kinase Inhibitor p16; D004334:Drug Administration Schedule; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D007274:Injections, Intraperitoneal; D058185:Magnetite Nanoparticles / Q000008:administration & dosage* / Q000737:chemistry; D051379:Mice; D009363:Neoplasm Proteins / Q000235:genetics* / Q000378:metabolism; D010316:Particle Size; D016159:Tumor Suppressor Protein p53 / Q000235:genetics* / Q000378:metabolism
D000970:Antineoplastic Agents; C000614131:CDKN2A protein, human; D019941:Cyclin-Dependent Kinase Inhibitor p16; D058185:Magnetite Nanoparticles; D009363:Neoplasm Proteins; C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53; D001205:Ascorbic Acid