Growth inhibition of insulin-like growth factor I receptor monoclonal antibody to human colorectal cancer cells. 2008

Youcheng Zhang, and Yawu Zhang
Department of General Surgery, Second Hospital of Lanzhou University, Lanzhou, Gansu Province, China.

OBJECTIVE Insulin-like growth factors (IGFs) and their receptors play a critical role in the growth and regulation of many type of malignant cells. The purpose of this study was to clarify the expression of Insulin-like growth factor I receptor (IGF-IR) in a human colorectal cancer cell line HT-29 and investigate the effects of 2 IGF-IR monoclonal antibodies (Mab) on the biological behavior of HT-29 cell line. METHODS Immunohistochemistry was used to test the expression of IGF-IR in HT-29 cell line, MTT assay was used to determine the antiproliferation effects of 2 kinds of IGF-IR monoclonal antibody on HT-29 cells. The effects of apoptosis rate and cell cycle of HT-29 cells were estimated by flow cytometry (FCM). RESULTS IGF-IR was expressed in the membranes of HT-29 cell line; MTT results show that each IGF-IR (alpha-Subunit)Ab-3 Mab group has remarkable difference (p < 0.01) as compared with control group, each IGF-IRalpha(1H7)L Mab group has no remarkable difference (p > 0.05) as compared with control group, each IGF-IRalpha(1H7)L Mab group has light antiproliferation effect on the HT-29 cells. IGF-IR(alpha-Subunit)Ab-3 has stronger antiproliferation effect on the HT-29 cells and dose-depended growth inhibition effects were observed when concentration is less than 1.5 ug/ml;The 2 kinds of IGF-IR monoclonal antibody can arrest the cell cycle at any phase of HT-29 cells and induce apoptosis. Under the incubating conditions of containing 5 percent fetal bovine serum (FCS) and no FCS, the apoptosis percentage of IGF-IR(alpha-Subunit)Ab-3 group and IGF-IRalpha(1H7)L group have obviously increased (p < 0.01). After the number of cells was increased 30 times, the apoptosis percentage of IGF-IR(alpha-Subunit)Ab-3 group and IGF-IRalpha(1H7)L group have no remarkable differences as compared with control group (p > 0.05). CONCLUSIONS Blockade of the IGF-IR with IGF-IR Mab inhibiting proliferation, arresting cell cycle and inducing apoptosis of HT-29 cells may represent a valid approach to inhibit tumor growth.

UI MeSH Term Description Entries
D007150 Immunohistochemistry Histochemical localization of immunoreactive substances using labeled antibodies as reagents. Immunocytochemistry,Immunogold Techniques,Immunogold-Silver Techniques,Immunohistocytochemistry,Immunolabeling Techniques,Immunogold Technics,Immunogold-Silver Technics,Immunolabeling Technics,Immunogold Silver Technics,Immunogold Silver Techniques,Immunogold Technic,Immunogold Technique,Immunogold-Silver Technic,Immunogold-Silver Technique,Immunolabeling Technic,Immunolabeling Technique,Technic, Immunogold,Technic, Immunogold-Silver,Technic, Immunolabeling,Technics, Immunogold,Technics, Immunogold-Silver,Technics, Immunolabeling,Technique, Immunogold,Technique, Immunogold-Silver,Technique, Immunolabeling,Techniques, Immunogold,Techniques, Immunogold-Silver,Techniques, Immunolabeling
D002453 Cell Cycle The complex series of phenomena, occurring between the end of one CELL DIVISION and the end of the next, by which cellular material is duplicated and then divided between two daughter cells. The cell cycle includes INTERPHASE, which includes G0 PHASE; G1 PHASE; S PHASE; and G2 PHASE, and CELL DIVISION PHASE. Cell Division Cycle,Cell Cycles,Cell Division Cycles,Cycle, Cell,Cycle, Cell Division,Cycles, Cell,Cycles, Cell Division,Division Cycle, Cell,Division Cycles, Cell
D005434 Flow Cytometry Technique using an instrument system for making, processing, and displaying one or more measurements on individual cells obtained from a cell suspension. Cells are usually stained with one or more fluorescent dyes specific to cell components of interest, e.g., DNA, and fluorescence of each cell is measured as it rapidly transverses the excitation beam (laser or mercury arc lamp). Fluorescence provides a quantitative measure of various biochemical and biophysical properties of the cell, as well as a basis for cell sorting. Other measurable optical parameters include light absorption and light scattering, the latter being applicable to the measurement of cell size, shape, density, granularity, and stain uptake. Cytofluorometry, Flow,Cytometry, Flow,Flow Microfluorimetry,Fluorescence-Activated Cell Sorting,Microfluorometry, Flow,Cell Sorting, Fluorescence-Activated,Cell Sortings, Fluorescence-Activated,Cytofluorometries, Flow,Cytometries, Flow,Flow Cytofluorometries,Flow Cytofluorometry,Flow Cytometries,Flow Microfluorometries,Flow Microfluorometry,Fluorescence Activated Cell Sorting,Fluorescence-Activated Cell Sortings,Microfluorimetry, Flow,Microfluorometries, Flow,Sorting, Fluorescence-Activated Cell,Sortings, Fluorescence-Activated Cell
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000911 Antibodies, Monoclonal Antibodies produced by a single clone of cells. Monoclonal Antibodies,Monoclonal Antibody,Antibody, Monoclonal
D015179 Colorectal Neoplasms Tumors or cancer of the COLON or the RECTUM or both. Risk factors for colorectal cancer include chronic ULCERATIVE COLITIS; FAMILIAL POLYPOSIS COLI; exposure to ASBESTOS; and irradiation of the CERVIX UTERI. Colorectal Cancer,Colorectal Carcinoma,Colorectal Tumors,Neoplasms, Colorectal,Cancer, Colorectal,Cancers, Colorectal,Carcinoma, Colorectal,Carcinomas, Colorectal,Colorectal Cancers,Colorectal Carcinomas,Colorectal Neoplasm,Colorectal Tumor,Neoplasm, Colorectal,Tumor, Colorectal,Tumors, Colorectal
D017209 Apoptosis A regulated cell death mechanism characterized by distinctive morphologic changes in the nucleus and cytoplasm, including the endonucleolytic cleavage of genomic DNA, at regularly spaced, internucleosomal sites, i.e., DNA FRAGMENTATION. It is genetically programmed and serves as a balance to mitosis in regulating the size of animal tissues and in mediating pathologic processes associated with tumor growth. Apoptosis, Extrinsic Pathway,Apoptosis, Intrinsic Pathway,Caspase-Dependent Apoptosis,Classic Apoptosis,Classical Apoptosis,Programmed Cell Death,Programmed Cell Death, Type I,Apoptoses, Extrinsic Pathway,Apoptoses, Intrinsic Pathway,Apoptosis, Caspase-Dependent,Apoptosis, Classic,Apoptosis, Classical,Caspase Dependent Apoptosis,Cell Death, Programmed,Classic Apoptoses,Extrinsic Pathway Apoptoses,Extrinsic Pathway Apoptosis,Intrinsic Pathway Apoptoses,Intrinsic Pathway Apoptosis
D017526 Receptor, IGF Type 1 A protein-tyrosine kinase receptor that is closely related in structure to the INSULIN RECEPTOR. Although commonly referred to as the IGF-I receptor, it binds both IGF-I and IGF-II with high affinity. It is comprised of a tetramer of two alpha and two beta subunits which are derived from cleavage of a single precursor protein. The beta subunit contains an intrinsic tyrosine kinase domain. IGF Type 1 Receptor,IGF-I Receptor,Receptor, IGF-I,Receptor, Insulin-Like Growth Factor I,Receptor, Insulin-Like Growth Factor Type 1,IGF-1 Receptor,Insulin-Like-Growth Factor I Receptor,Receptor, IGF Type 1 alpha Subunit,Receptor, IGF Type 1 beta Subunit,Receptors, IGF-1,Receptors, Insulin-Like-Growth Factor I,IGF 1 Receptor,IGF I Receptor,IGF-1 Receptors,Insulin Like Growth Factor I Receptor,Receptor, IGF I,Receptor, IGF-1,Receptors, IGF 1
D049109 Cell Proliferation All of the processes involved in increasing CELL NUMBER including CELL DIVISION. Cell Growth in Number,Cellular Proliferation,Cell Multiplication,Cell Number Growth,Growth, Cell Number,Multiplication, Cell,Number Growth, Cell,Proliferation, Cell,Proliferation, Cellular
D019073 HT29 Cells Human colonic ADENOCARCINOMA cells that are able to express differentiation features characteristic of mature intestinal cells such as the GOBLET CELLS. HT-29 Cells,Cell, HT-29,Cell, HT29,Cells, HT-29,Cells, HT29,HT 29 Cells,HT-29 Cell,HT29 Cell

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