Bzd9l1: Elucidation Of Its Anti-angiogenic Potential In In-vitro And In-vivo Colorectal Cancer Models

Colorectal cancer (CRC) is the third most common cancer globally. CRC depends largely on angiogenesis for growth and metastasis. Much effort has been made to selectively target the angiogenic pathways to restrain tumour growth. However, some CRC patients become resilient to these anti-angiogenic dru...

Full description

Saved in:

Bibliographic Details
Main Author:	Subramaniam, Ayappa V.
Format:	Thesis
Language:	English
Published:	2023
Subjects:	R5-920 Medicine (General)
Online Access:	http://eprints.usm.my/60307/1/AYAPPA%20AL%20V.SUBRAMANIAM%20-%20TESIS24.pdf
Tags:	Add Tag No Tags, Be the first to tag this record!

id	my-usm-ep.60307
record_format	uketd_dc
spelling	my-usm-ep.603072024-03-29T09:14:19Z Bzd9l1: Elucidation Of Its Anti-angiogenic Potential In In-vitro And In-vivo Colorectal Cancer Models 2023-09 Subramaniam, Ayappa V. R5-920 Medicine (General) Colorectal cancer (CRC) is the third most common cancer globally. CRC depends largely on angiogenesis for growth and metastasis. Much effort has been made to selectively target the angiogenic pathways to restrain tumour growth. However, some CRC patients become resilient to these anti-angiogenic drugs and standard therapies. The class III histone deacetylase family of sirtuins (SIRTs) has been closely linked to cancer progression but less is known about its activity in regulating tumour angiogenesis. BZD9L1 is a novel sirtuin inhibitor with demonstrated anti-cancer activities. This study aimed to investigate the anti-angiogenic potential of BZD9L1 on EA.hy926 endothelial cells (EC) in vitro and HCT116 tumour xenograft nude mice. The in vitro experiments comprised of cell viability assay, scratch wound assay, tube formation assay, spheroid sprouting assay, western blotting, angiogenesis array, cell cycle and apoptosis analysis via flow cytometry and finally, indirect co-culture model. Nude mice tumour xenograft model was used for the in vivo study, where hematoxylin and eosin staining was done to study the percentage of necrosis in the tumour section and immunohistochemistry was conducted to investigate the protein expression of Ki67 and CD34. BZD9L1 was shown to reduce cell viability, cell migration, tube formation, and spheroid sprouting of EC. BZD9L1 at 10μM was also shown to inhibit SIRT2 and SIRT3 protein in EA.hy926 cells. Angiogenesis array results revealed that the compound reduces the cytokine concentration of Angiogenin, bFGF, PDGF-BB, and PIGF significantly (P * < 0.05) compared to the control group 2023-09 Thesis http://eprints.usm.my/60307/ http://eprints.usm.my/60307/1/AYAPPA%20AL%20V.SUBRAMANIAM%20-%20TESIS24.pdf application/pdf en public phd doctoral Universiti Sains Malaysia Institut Penyelidikan Perubatan Molekul
institution	Universiti Sains Malaysia
collection	USM Institutional Repository
language	English
topic	R5-920 Medicine (General)
spellingShingle	R5-920 Medicine (General) Subramaniam, Ayappa V. Bzd9l1: Elucidation Of Its Anti-angiogenic Potential In In-vitro And In-vivo Colorectal Cancer Models
description	Colorectal cancer (CRC) is the third most common cancer globally. CRC depends largely on angiogenesis for growth and metastasis. Much effort has been made to selectively target the angiogenic pathways to restrain tumour growth. However, some CRC patients become resilient to these anti-angiogenic drugs and standard therapies. The class III histone deacetylase family of sirtuins (SIRTs) has been closely linked to cancer progression but less is known about its activity in regulating tumour angiogenesis. BZD9L1 is a novel sirtuin inhibitor with demonstrated anti-cancer activities. This study aimed to investigate the anti-angiogenic potential of BZD9L1 on EA.hy926 endothelial cells (EC) in vitro and HCT116 tumour xenograft nude mice. The in vitro experiments comprised of cell viability assay, scratch wound assay, tube formation assay, spheroid sprouting assay, western blotting, angiogenesis array, cell cycle and apoptosis analysis via flow cytometry and finally, indirect co-culture model. Nude mice tumour xenograft model was used for the in vivo study, where hematoxylin and eosin staining was done to study the percentage of necrosis in the tumour section and immunohistochemistry was conducted to investigate the protein expression of Ki67 and CD34. BZD9L1 was shown to reduce cell viability, cell migration, tube formation, and spheroid sprouting of EC. BZD9L1 at 10μM was also shown to inhibit SIRT2 and SIRT3 protein in EA.hy926 cells. Angiogenesis array results revealed that the compound reduces the cytokine concentration of Angiogenin, bFGF, PDGF-BB, and PIGF significantly (P * < 0.05) compared to the control group
format	Thesis
qualification_name	Doctor of Philosophy (PhD.)
qualification_level	Doctorate
author	Subramaniam, Ayappa V.
author_facet	Subramaniam, Ayappa V.
author_sort	Subramaniam, Ayappa V.
title	Bzd9l1: Elucidation Of Its Anti-angiogenic Potential In In-vitro And In-vivo Colorectal Cancer Models
title_short	Bzd9l1: Elucidation Of Its Anti-angiogenic Potential In In-vitro And In-vivo Colorectal Cancer Models
title_full	Bzd9l1: Elucidation Of Its Anti-angiogenic Potential In In-vitro And In-vivo Colorectal Cancer Models
title_fullStr	Bzd9l1: Elucidation Of Its Anti-angiogenic Potential In In-vitro And In-vivo Colorectal Cancer Models
title_full_unstemmed	Bzd9l1: Elucidation Of Its Anti-angiogenic Potential In In-vitro And In-vivo Colorectal Cancer Models
title_sort	bzd9l1: elucidation of its anti-angiogenic potential in in-vitro and in-vivo colorectal cancer models
granting_institution	Universiti Sains Malaysia
granting_department	Institut Penyelidikan Perubatan Molekul
publishDate	2023
url	http://eprints.usm.my/60307/1/AYAPPA%20AL%20V.SUBRAMANIAM%20-%20TESIS24.pdf
_version_	1804888909443760128

Bzd9l1: Elucidation Of Its Anti-angiogenic Potential In In-vitro And In-vivo Colorectal Cancer Models

Similar Items