Back to Journals » International Journal of Nanomedicine » Volume 8 » Issue 1

The cooperative effect of p53 and Rb in local nanotherapy in a rabbit VX2 model of hepatocellular carcinoma

Authors Dong S, Tang Q, Long M, Guan J, Ye L, Li G

Received 10 July 2013

Accepted for publication 1 August 2013

Published 2 October 2013 Volume 2013:8(1) Pages 3757—3768

DOI https://doi.org/10.2147/IJN.S51353

Checked for plagiarism Yes

Review by Single-blind

Peer reviewer comments 4

Shengli Dong,1 Qibin Tang,2 Miaoyun Long,3 Jian Guan,4 Lu Ye,5 Gaopeng Li6

1Department of General Surgery, The Second Hospital of Shanxi Medical University, Shanxi Medical University, Taiyuan, Shanxi Province, 2Department of Hepatobiliopancreatic Surgery, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, Guangdong Province, 3Department of Thyroid and Vascular Surgery, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, Guangdong Province, 4Department of Radiology, First Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong Province, 5Infection Department, Guangzhou No 8 Hospital, Guangzhou, Guangdong Province, 6Department of Ultrasound, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, Guangdong Province, People's Republic of China

Background/aim: A local nanotherapy (LNT) combining the therapeutic efficacy of trans-arterial embolization, nanoparticles, and p53 gene therapy has been previously presented. The study presented here aimed to further improve the incomplete tumor eradication and limited survival enhancement and to elucidate the molecular mechanism of the LNT.
Methods: In a tumor-targeting manner, recombinant expressing plasmids harboring wild-type p53 and Rb were either co-transferred or transferred separately to rabbit hepatic VX2 tumors in a poly-L-lysine-modified hydroxyapatite nanoparticle nanoplex and Lipiodol® (Guerbet, Villepinte, France) emulsion via the hepatic artery. Subsequent co-expression of p53 and Rb proteins within the treated tumors was investigated by Western blotting and in situ analysis by laser-scanning confocal microscopy. The therapeutic effect was evaluated by the tumor growth velocity, apoptosis and necrosis rates, their sensitivity to Adriamycin® (ADM), mitomycin C, and fluorouracil, the microvessel density of tumor tissue, and the survival time of animals. Eventually, real-time polymerase chain reaction and enhanced chemiluminescence Western blotting were used to investigate the expressive changes of important genes related to the therapy.
Results: The administration procedure proved safe for the rabbits' liver function, the p53 plus Rb LNT showed significantly better antitumoral effect and lower expression of malignant genes than the p53 or Rb LNT, although no significant difference was observed in animal survival when the p53 plus Rb LNT was compared with the p53 LNT.
Conclusion: Rb works synergistically with p53 in combined therapy mediated by a poly-L-lysine-modified hydroxyapatite nanoparticle nanoplex to augment the antitumoral effect through the downregulated expression of important genes related to apoptosis, necrosis, growth, differentiation and multidrug resistance of tumor cells. LNT with p53 and Rb is potentially an effective antitumor therapy for hepatocellular carcinoma.

Keywords: nanoparticles, gene-transfer techniques, targeting, combined therapy

Creative Commons License This work is published and licensed by Dove Medical Press Limited. The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution - Non Commercial (unported, v3.0) License. By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. For permission for commercial use of this work, please see paragraphs 4.2 and 5 of our Terms.

Download Article [PDF]  View Full Text [HTML][Machine readable]

 

Readers of this article also read:

Intradermal air pouch leukocytosis as an in vivo test for nanoparticles

Vandooren J, Berghmans N, Dillen C, Van Aelst I, Ronsse I, Israel LL, Rosenberger I, Kreuter J, Lellouche JP, Michaeli S, Locatelli E, Comes Franchini M, Aiertza MK, Sánchez-Abella L, Loinaz I, Edwards DR, Shenkman L, Opdenakker G

International Journal of Nanomedicine 2013, 8:4745-4756

Published Date: 13 December 2013

Vincristine sulfate liposomal injection for acute lymphoblastic leukemia

Soosay Raj TA, Smith AM, Moore AS

International Journal of Nanomedicine 2013, 8:4361-4369

Published Date: 6 November 2013

Synthesis and characterization of surface-enhanced Raman-scattered gold nanoparticles

Kalmodia S, Harjwani J, Rajeswari R, Yang W, Barrow CJ, Ramaprabhu S, Krishnakumar S, Elchuri SV

International Journal of Nanomedicine 2013, 8:4327-4338

Published Date: 6 November 2013

Local delivery of controlled-release simvastatin/PLGA/HAp microspheres enhances bone repair

Tai IC, Fu YC, Wang CK, Chang JK, Ho ML

International Journal of Nanomedicine 2013, 8:3895-3905

Published Date: 11 October 2013

Targeted hyperthermia after selective embolization with ferromagnetic nanoparticles in a VX2 rabbit liver tumor model

Sun HL, Xu LF, Fan TY, Zhang HZ, Wang XD, Zhou YF, Yang RJ

International Journal of Nanomedicine 2013, 8:3795-3804

Published Date: 2 October 2013

Biodistribution, kinetics, and biological fate of SPION microbubbles in the rat

Barrefelt A, Saghafian M, Kuiper R, Ye F, Egri G, Klickermann M, Brismar TB, Aspelin P, Muhammed M, Dähne L, Hassan M

International Journal of Nanomedicine 2013, 8:3241-3254

Published Date: 26 August 2013

Systematic dielectrophoretic analysis of the Ara C induced NB4 cell apoptosis combined with gene expression profiling

Lv Y, Zeng L, Zhang G, Xu Y, Lu Y, Mitchelson K, Cheng J, Xing W

International Journal of Nanomedicine 2013, 8:2333-2350

Published Date: 28 June 2013

One-step detection of circulating tumor cells in ovarian cancer using enhanced fluorescent silica nanoparticles

Kim JH, Chung HH, Jeong MS, Song MR, Kang KW, Kim JS

International Journal of Nanomedicine 2013, 8:2247-2257

Published Date: 21 June 2013