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 |
Externí odkaz: |