Effects of immunisation against PCSK9 in mice bearing melanoma

Introduction Inhibition of proprotein convertase subtilisin/kexin 9 (PCSK9) is an established modality for the treatment of hypercholesterolaemia. However, the impact of PCSK9 inhibition in other situations such as cancer remains largely unknown. The current study was conducted to study the effects...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Amir Abbas Momtazi-Borojeni, Maryam Ebrahimi Nik, Mahmoud Reza Jaafari, Maciej Banach, Amirhossein Sahebkar
Formato:	article
Lenguaje:	EN
Publicado:	Termedia Publishing House 2019
Materias:	cancer melanoma vaccine nanoparticle immunization liposome pcsk9 immunisation Medicine R
Acceso en línea:	https://doaj.org/article/6dd2f54a36384257a4141794031b4087
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:6dd2f54a36384257a4141794031b4087
record_format	dspace
spelling	oai:doaj.org-article:6dd2f54a36384257a4141794031b40872021-12-02T18:33:05ZEffects of immunisation against PCSK9 in mice bearing melanoma1734-19221896-915110.5114/aoms.2020.91291https://doaj.org/article/6dd2f54a36384257a4141794031b40872019-12-01T00:00:00Zhttps://www.archivesofmedicalscience.com/Effects-of-immunisation-against-PCSK9-in-mice-bearing-melanoma,110730,0,2.htmlhttps://doaj.org/toc/1734-1922https://doaj.org/toc/1896-9151Introduction Inhibition of proprotein convertase subtilisin/kexin 9 (PCSK9) is an established modality for the treatment of hypercholesterolaemia. However, the impact of PCSK9 inhibition in other situations such as cancer remains largely unknown. The current study was conducted to study the effects of PCSK9 inhibition on cancer endpoints in mice bearing melanoma. Material and methods To generate antiPCSK9 antibody in vivo, a nanoliposomal antiPCSK9 vaccine adsorbed to 0.4% Alum adjuvant was subcutaneously injected in C57BL/6 mice four times with bi-weekly intervals. Two weeks after the last immunisation, mice were subcutaneously inoculated with B16F0 melanoma cells. After a tumour mass was palpable (approximately 10 mm3), the mice were randomly divided into four groups and subjected to different treatment protocols: (1) PBS (untreated control), (2) vaccine group, (3) the combination of vaccine and a single dose of liposomal doxorubicin (Doxil®), and (4) liposomal doxorubicin (positive control) group. To determine therapeutic efficacy, mouse body weight, tumour size, and survival were monitored every three days for 36 days. Results The nanoliposomal antiPCSK9 vaccine was found to efficiently induce specific antibodies against PCSK9 in C57BL/6 mice, thereby reducing plasma levels and function of PCSK9. Tumour volumes in the vaccinated group were not significantly different from those in the liposomal doxorubicin, combination, and control groups. The time to reach endpoint (TTE) values of the vaccine (28 ±5 days), combination (30 ±6 days), liposomal doxorubicin (34 ±2 days), and control (31 ±2 days) groups were not significantly different, either. Furthermore, the tumour growth delay (TGD) values of the vaccine (–11.5 ±15.4%), liposomal doxorubicin (7.75 ±6.5%), combination (–6 ±20.77%), and control (0 ±7.5) groups were not significantly different. Finally, there was no significant difference between the median survival time and lifespan of the vaccinated versus other tested groups. Conclusions The nanoliposomal PCSK9 vaccine did not adversely affect the growth of melanoma tumour nor the survival of tumour-bearing mice.Amir Abbas Momtazi-BorojeniMaryam Ebrahimi NikMahmoud Reza JaafariMaciej BanachAmirhossein SahebkarTermedia Publishing Housearticlecancermelanomavaccinenanoparticleimmunizationliposomepcsk9immunisationMedicineRENArchives of Medical Science, Vol 16, Iss 1, Pp 189-199 (2019)
institution	DOAJ
collection	DOAJ
language	EN
topic	cancer melanoma vaccine nanoparticle immunization liposome pcsk9 immunisation Medicine R
spellingShingle	cancer melanoma vaccine nanoparticle immunization liposome pcsk9 immunisation Medicine R Amir Abbas Momtazi-Borojeni Maryam Ebrahimi Nik Mahmoud Reza Jaafari Maciej Banach Amirhossein Sahebkar Effects of immunisation against PCSK9 in mice bearing melanoma
description	Introduction Inhibition of proprotein convertase subtilisin/kexin 9 (PCSK9) is an established modality for the treatment of hypercholesterolaemia. However, the impact of PCSK9 inhibition in other situations such as cancer remains largely unknown. The current study was conducted to study the effects of PCSK9 inhibition on cancer endpoints in mice bearing melanoma. Material and methods To generate antiPCSK9 antibody in vivo, a nanoliposomal antiPCSK9 vaccine adsorbed to 0.4% Alum adjuvant was subcutaneously injected in C57BL/6 mice four times with bi-weekly intervals. Two weeks after the last immunisation, mice were subcutaneously inoculated with B16F0 melanoma cells. After a tumour mass was palpable (approximately 10 mm3), the mice were randomly divided into four groups and subjected to different treatment protocols: (1) PBS (untreated control), (2) vaccine group, (3) the combination of vaccine and a single dose of liposomal doxorubicin (Doxil®), and (4) liposomal doxorubicin (positive control) group. To determine therapeutic efficacy, mouse body weight, tumour size, and survival were monitored every three days for 36 days. Results The nanoliposomal antiPCSK9 vaccine was found to efficiently induce specific antibodies against PCSK9 in C57BL/6 mice, thereby reducing plasma levels and function of PCSK9. Tumour volumes in the vaccinated group were not significantly different from those in the liposomal doxorubicin, combination, and control groups. The time to reach endpoint (TTE) values of the vaccine (28 ±5 days), combination (30 ±6 days), liposomal doxorubicin (34 ±2 days), and control (31 ±2 days) groups were not significantly different, either. Furthermore, the tumour growth delay (TGD) values of the vaccine (–11.5 ±15.4%), liposomal doxorubicin (7.75 ±6.5%), combination (–6 ±20.77%), and control (0 ±7.5) groups were not significantly different. Finally, there was no significant difference between the median survival time and lifespan of the vaccinated versus other tested groups. Conclusions The nanoliposomal PCSK9 vaccine did not adversely affect the growth of melanoma tumour nor the survival of tumour-bearing mice.
format	article
author	Amir Abbas Momtazi-Borojeni Maryam Ebrahimi Nik Mahmoud Reza Jaafari Maciej Banach Amirhossein Sahebkar
author_facet	Amir Abbas Momtazi-Borojeni Maryam Ebrahimi Nik Mahmoud Reza Jaafari Maciej Banach Amirhossein Sahebkar
author_sort	Amir Abbas Momtazi-Borojeni
title	Effects of immunisation against PCSK9 in mice bearing melanoma
title_short	Effects of immunisation against PCSK9 in mice bearing melanoma
title_full	Effects of immunisation against PCSK9 in mice bearing melanoma
title_fullStr	Effects of immunisation against PCSK9 in mice bearing melanoma
title_full_unstemmed	Effects of immunisation against PCSK9 in mice bearing melanoma
title_sort	effects of immunisation against pcsk9 in mice bearing melanoma
publisher	Termedia Publishing House
publishDate	2019
url	https://doaj.org/article/6dd2f54a36384257a4141794031b4087
work_keys_str_mv	AT amirabbasmomtaziborojeni effectsofimmunisationagainstpcsk9inmicebearingmelanoma AT maryamebrahiminik effectsofimmunisationagainstpcsk9inmicebearingmelanoma AT mahmoudrezajaafari effectsofimmunisationagainstpcsk9inmicebearingmelanoma AT maciejbanach effectsofimmunisationagainstpcsk9inmicebearingmelanoma AT amirhosseinsahebkar effectsofimmunisationagainstpcsk9inmicebearingmelanoma
_version_	1718377925336629248

Effects of immunisation against PCSK9 in mice bearing melanoma

Ejemplares similares