Anti-Tumor Effects of Bak-Proteoliposomes against Glioblastoma.
Despite palliative treatments, glioblastoma (GBM) remains a devastating malignancy with a mean survival of about 15 months after diagnosis. Programmed cell-death is de-regulated in almost all GBM and the re-activation of the mitochondrial apoptotic pathway through exogenous bioactive proteins may represent a powerful therapeutic tool to treat multidrug resistant GBM. We have reported that human Bak protein integrated in Liposomes (LB) was able, in vitro, to activate the mitochondrial apoptotic pathway in colon cancer cells. To evaluate the anti-tumor effects of LB on GBM, MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assays and Western blot analysis were performed on GL26 murine cell line. LB treatment shows a dose-dependent inhibition of cell viability, followed by an up-regulation of Bax and a down-modulation of JNK1 proteins. In GL26-bearing mice, two different routes of administration were tested: intra-tumor and intravenous. Biodistribution, tumor growth and animal survival rates were followed. LB show long-lasting tumor accumulation. Moreover, the intra-tumor administration of LB induces tumor growth delay and total tumor regression in about 40% of treated mice, while the intravenous injection leads to a significant increased life span of mice paralleled by an increased tumor cells apoptosis. Our findings are functional to the design of LB with potentiated therapeutic efficacy for GBM.
SyNaBi Laboratory, TIMC IMAG, UMR S5525, UJF/CNRS, Joseph Fourier University, Grenoble Cedex 9 38700, France. liguorilavinia@gmail.com.
Lavinia
L
Liguori
Laboratory of Oncology, Istituto Giannina Gaslini, Genoa 16147, Italy. fabiopastorino@ospedale-gaslini.ge.it.
Fabio
F
Pastorino
The Rex Laboratory, TIMC IMAG, UMR5525, UJF/CNRS, Joseph Fourier University, CHU-Grenoble, BP217, Grenoble Cedex 9 38043, France. xavier.rousset@gmail.com.
Xavier
X
Rousset
The Rex Laboratory, TIMC IMAG, UMR5525, UJF/CNRS, Joseph Fourier University, CHU-Grenoble, BP217, Grenoble Cedex 9 38043, France. silvialfn@gmail.com.
Silvia
S
Alfano
The Rex Laboratory, TIMC IMAG, UMR5525, UJF/CNRS, Joseph Fourier University, CHU-Grenoble, BP217, Grenoble Cedex 9 38043, France. sandra.cortes@synthelis.fr.
Sandra
S
Cortes
Animal Facility, IRCCS Azienda Ospedaliera Universitaria San Martino-IST, Genoa 16132, Italy. laura.emionite@hsanmartino.it.
Laura
L
Emionite
Laboratorio di Trasferimento Genico, IRCCS Azienda Ospedaliera Universitaria San Martino-IST, Genoa 16132, Italy. antonio.daga@hsanmartino.it.
Antonio
A
Daga
Laboratory of Oncology, Istituto Giannina Gaslini, Genoa 16147, Italy. mircoponzoni@ospedale-gaslini.ge.it.
Mirco
M
Ponzoni
The Rex Laboratory, TIMC IMAG, UMR5525, UJF/CNRS, Joseph Fourier University, CHU-Grenoble, BP217, Grenoble Cedex 9 38043, France. jllenormand@chu-grenoble.fr.
Jean-Luc
JL
Lenormand
D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D005909:Glioblastoma / Q000188:drug therapy*; D006801:Humans; D008081:Liposomes; D051379:Mice; D011510:Proteolipids / Q000737:chemistry*; D050998:bcl-2 Homologous Antagonist-Killer Protein / Q000737:chemistry*
D000970:Antineoplastic Agents; C494772:BAK1 protein, human; D008081:Liposomes; D011510:Proteolipids; D050998:bcl-2 Homologous Antagonist-Killer Protein; C020485:proteoliposomes
Bak; glioblastoma; proteoliposomes; recombinant membrane protein