Suppression of Colorectal Cancer Liver Metastasis by Apolipoprotein(a) Kringle V in a Nude Mouse Model through the Induction of Apoptosis in Tumor-Associated Endothelial Cells

Autor: Sun Jin Kim, Jin Hyung Ahn, Hyun Kyung Yu, Ho Jeong Lee, Jang Seong Kim, Soon Won Hong
Rok vydání: 2014
Předmět:
Pathology
Angiogenesis
Colorectal cancer
Cancer Treatment
lcsh:Medicine
Gene Expression
Apoptosis
Biochemistry
Epithelium
Umbilical vein
Metastasis
Mice
RNA interference
Nude mouse
Kringles
Molecular Cell Biology
Gastrointestinal Cancers
Basic Cancer Research
Drug Discovery
Medicine and Health Sciences
Medicine
lcsh:Science
Endoplasmic Reticulum Chaperone BiP
Energy-Producing Organelles
Multidisciplinary
Cell Death
Neovascularization
Pathologic
biology
Liver Neoplasms
Animal Models
Oncology
Cell Processes
Epigenetics
Antiangiogenesis Therapy
Fluorouracil
Anatomy
Cellular Types
Antibody
Colorectal Neoplasms
Research Article
medicine.medical_specialty
Drug Research and Development
Lipoproteins
Mice
Nude
Mouse Models
Gastroenterology and Hepatology
Bioenergetics
Mouse model of colorectal and intestinal cancer
Research and Analysis Methods
Rectal Cancer
Model Organisms
Cell Line
Tumor
Gastrointestinal Tumors
Genetics
Human Umbilical Vein Endothelial Cells
Animals
Apolipoproteins A
Pharmacology
Biology and life sciences
business.industry
lcsh:R
Endothelial Cells
Proteins
Cancers and Neoplasms
Epithelial Cells
Cell Biology
biology.organism_classification
medicine.disease
Biological Tissue
Apolipoproteins
biology.protein
lcsh:Q
business
Zdroj: PLoS ONE
PLoS ONE, Vol 9, Iss 4, p e93794 (2014)
ISSN: 1932-6203
Popis: The formation of liver metastases in colorectal cancer patients is the primary cause of patient death. Current therapies directed at liver metastasis from colorectal cancer have had minimal impact on patient outcomes. Therefore, the development of alternative treatment strategies for liver metastasis is needed. In the present study, we demonstrated that recombinant human apolipoprotein(a) kringle V, also known as rhLK8, induced the apoptotic turnover of endothelial cells in vitro through the mitochondrial apoptosis pathway. The interaction of rhLK8 with glucose-regulated protein 78 (GRP78) may be involved in the induction of apoptosis because the inhibition of GRP78 by GRP78-specific antibodies or siRNA knockdown inhibited the rhLK8-mediated apoptosis of human umbilical vein endothelial cells in vitro. Next, to evaluate the effects of rhLK8 on angiogenesis and metastasis, an experimental model of liver metastasis was established by injecting a human colorectal cancer cell line, LS174T, into the spleens of BALB/c nude mice. The systemic administration of rhLK8 significantly suppressed liver metastasis from human colorectal cancer cells and improved host survival compared with controls. The combination of rhLK8 and 5-fluorouracil substantially increased these survival benefits compared with either therapy alone. Histological observation showed significant induction of apoptosis among tumor-associated endothelial cells in liver metastases from rhLK8-treated mice compared with control mice. Collectively, these results suggest that the combination of rhLK8 with conventional chemotherapy may be a promising approach for the treatment of patients with life-threatening colorectal cancer liver metastases.
Databáze: OpenAIRE
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