ABSTRACT
Apigenin is a naturally occurring compound with anti-inflammatory, antioxidant, and anticancer properties. In this study, we investigated the effects of apigenin on migration and metastasis in experimental human hepatocellular carcinoma (HCC) cell lines in vitro and in vivo. Apigenin dose-dependently inhibited proliferation, migration, and invasion by PLC and Bel-7402 human HCC cells. It also suppressed tumor growth in PLC cell xenografts without altering body weight, thereby prolonging survival. Apigenin reduced Snai1 and NF-κB expression, reversed increases in epithelial-mesenchymal transition (EMT) marker levels, increased cellular adhesion, regulated actin polymerization and cell migration, and inhibited invasion and migration by HCC cells. Apigenin may therefore inhibit EMT by inhibiting the NF-κB/Snail pathway in human HCC.
Subject(s)
Apigenin/pharmacology , Carcinoma, Hepatocellular/pathology , Epithelial-Mesenchymal Transition/drug effects , Liver Neoplasms/pathology , NF-kappa B/metabolism , Snail Family Transcription Factors/metabolism , Animals , Carcinoma, Hepatocellular/metabolism , Cell Line, Tumor , Cell Movement/drug effects , Female , Hep G2 Cells , Humans , Liver Neoplasms/metabolism , Mice , Mice, Inbred BALB C , Mice, Nude , Neoplasm Metastasis , Signal Transduction/drug effectsABSTRACT
The cancer stem cell (CSC) theory holds that a minority population within tumors possesses stem cell properties of self-renewal and multilineage differentiation capacity and provides the initiating cells from which tumors are derived and sustained. However, verifying the existence of these CSCs has been a significant challenge. The CD133 antigen is a pentaspan membrane glycoprotein proposed to be a CSC marker for cancer-initiating subpopulations in the brain, colon and various other tissues. Here, CD133+ cells were obtained and characterized from the HT1080 cell line to determine the utility of this marker for isolating CSCs from human fibrosarcoma cells. In this study, CD133+ cells were separated from HT1080 cells using magnetic beads and characterized for their proliferation rate and resistance to chemotherapeutic drugs, cisplatin and doxorubicin, by MTS assay. Relative expression of tumor-associated genes Sox2, Oct3/4, Nanog, c-Myc, Bmi-1 and ABCG2 was measured by real-time polymerase chain reaction (PCR). Clonal sphere formation and the ability of CD133+ cells to initiate tumors in BALB/c nude mice was also evaluated. We found that CD133+ cells showed a high proliferation rate, increased resistance to chemotherapy drugs and overexpression of tumor-associated genes compared with these features in CD133- cells. Additionally, CD133+ cells were able to form spherical clusters in serum-free medium with high clonogenic efficiency, indicating a significantly greater tumor-initiating potential when compared with CD133- cells. These findings indicate that CD133+ cells identified within the HT1080 human fibrosarcoma cell line possess many CSC properties and may facilitate the development of improved therapies for fibrosarcoma.
Subject(s)
Antigens, CD/biosynthesis , Fibrosarcoma/metabolism , Fibrosarcoma/pathology , Glycoproteins/biosynthesis , Neoplastic Stem Cells/pathology , AC133 Antigen , ATP Binding Cassette Transporter, Subfamily G, Member 2 , ATP-Binding Cassette Transporters/genetics , Animals , Antigens, CD/genetics , Cell Line, Tumor , Cell Proliferation/drug effects , Cell Transformation, Neoplastic/genetics , Cell Transformation, Neoplastic/pathology , Cisplatin/pharmacology , Doxorubicin/pharmacology , Drug Resistance, Neoplasm/genetics , Fibrosarcoma/drug therapy , Fibrosarcoma/genetics , Glycoproteins/genetics , Homeodomain Proteins/genetics , Humans , Mice , Mice, Inbred BALB C , Mice, Nude , Nanog Homeobox Protein , Neoplasm Proteins/genetics , Neoplastic Stem Cells/drug effects , Octamer Transcription Factor-3/genetics , Peptides/genetics , Polycomb Repressive Complex 1/genetics , Proto-Oncogene Proteins c-myc/genetics , SOXB1 Transcription Factors/genetics , Spheroids, Cellular/pathologyABSTRACT
OBJECTIVE: To evaluate the effect on increasing bone cement-bone interface micro-gomphosis intensity with bone cement oscillator. METHODS: One hundred femoral bones of adult pig were randomly divided into 6 groups: oscillating group (A1) and control group (A2) of anti-tensile force, oscillating group (B1) and control group (B2) of anti-pressure (n = 20 in each group), oscillating group (C1) and control group (C2) of imaging (n = 10 in each group). Mechanics and CT test was performed, micro-gomphosis intensity of bone cement-bone interface between oscillating group and control group was compared. RESULTS: Mechanics and CT test showed bone cement-bone interface micro-gomphosis intensity in oscillating group was significantly stronger than control group (P < 0.01). CONCLUSION: Bone cement oscillator can significantly increase micro-gomphosis intensity of bone-cement interface, and reduce long-term aseptic loosening of artificial prostheses.
