Biomaterial Database

[Induction of apoptosis by mifepristone in androgen-independent prostate cancer cell lines in vitro]. 2006

Hui Zhang, and Jia-ju Lü, and Qing-zhen Gao, and Jie Zhang

Department of Urology, Shandong Provincial Hospital, Shandong University, Jinan 250021, China.

OBJECTIVE To investigate the effects of mifepristone on cell proliferation of human androgen-independent prostate carcinoma cell lines DU-145, PC-3 in vitro and the possible mechanisms involved. METHODS The A values of the prostate cancer cells DU-145 and PC-3 in each group with various concentrations (1, 10, 50, 100 micromol/L) of mifepristone at various time intervals (24-120 h) were detected with the colorimetric 3-(4, 5-dimethyl-2-thiazolyl)-2, 5-diphenyl tetrazolium bromide assay. The apoptosis rates of the DU-145 and PC-3 cells treated with 10 micromol/L of mifepristone for 24 h and 48 h were assessed by flow cytometry analysis technique. Immunohistochemical technique was used to determine the expression of bax, bcl-2 and vascular endothelial growth factor (VEGF) proteins after treatment with 10 micromol/L of mifepristone. RESULTS The A values of the cancer cells treated with 1 micromol/L of mifepristone were similar to that of controls, while those of the cells treated with 10 micromol/L, 50 micromol/L and 100 micromol/L of mifepristone were significantly different from that of controls (P < 0.01). Mifepristone markedly inhibited cell proliferation of prostate cancer cells DU-145 and PC-3 on a dose- and time-depending manner. The apoptosis rates of 10 micromol/L mifepristone for DU-145 cell line at 24 h, 48 h were respectively 15.3%, 30.4% with flow cytometry method and then PC-3 cell line were respectively 22.2%, 32.0%. Immunohistochemical technique showed the expression of bcl-2 and VEGF in the DU-145 and PC-3 cells treated with 10 micromol/L of mifepristone were significantly decreased, and the expression of bax was increased. CONCLUSIONS Mifepristone can induce apoptosis of androgen-independent prostate cancer cell lines DU-145 and PC-3 in vitro. The apoptosis effect is time-and-dose dependent. Mifepristone could initiate a cell death command via apoptotic pathways decreasing the expression of VEGF protein, downregulating the expression of bcl-2 protein and increasing the expression of bax protein.

UI	MeSH Term	Description	Entries
D008297	Male		Males
D011471	Prostatic Neoplasms	Tumors or cancer of the PROSTATE.	Cancer of Prostate,Prostate Cancer,Cancer of the Prostate,Neoplasms, Prostate,Neoplasms, Prostatic,Prostate Neoplasms,Prostatic Cancer,Cancer, Prostate,Cancer, Prostatic,Cancers, Prostate,Cancers, Prostatic,Neoplasm, Prostate,Neoplasm, Prostatic,Prostate Cancers,Prostate Neoplasm,Prostatic Cancers,Prostatic Neoplasm
D003124	Colorimetry	Any technique by which an unknown color is evaluated in terms of standard colors. The technique may be visual, photoelectric, or indirect by means of spectrophotometry. It is used in chemistry and physics. (McGraw-Hill Dictionary of Scientific and Technical Terms, 4th ed)
D004305	Dose-Response Relationship, Drug	The relationship between the dose of an administered drug and the response of the organism to the drug.	Dose Response Relationship, Drug,Dose-Response Relationships, Drug,Drug Dose-Response Relationship,Drug Dose-Response Relationships,Relationship, Drug Dose-Response,Relationships, Drug Dose-Response
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
D006727	Hormone Antagonists	Chemical substances which inhibit the function of the endocrine glands, the biosynthesis of their secreted hormones, or the action of hormones upon their specific sites.	Antagonists, Hormone
D006801	Humans	Members of the species Homo sapiens.	Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000728	Androgens	Compounds that interact with ANDROGEN RECEPTORS in target tissues to bring about the effects similar to those of TESTOSTERONE. Depending on the target tissues, androgenic effects can be on SEX DIFFERENTIATION; male reproductive organs, SPERMATOGENESIS; secondary male SEX CHARACTERISTICS; LIBIDO; development of muscle mass, strength, and power.	Androgen,Androgen Receptor Agonist,Androgen Effect,Androgen Effects,Androgen Receptor Agonists,Androgenic Agents,Androgenic Compounds,Agents, Androgenic,Agonist, Androgen Receptor,Agonists, Androgen Receptor,Compounds, Androgenic,Effect, Androgen,Effects, Androgen,Receptor Agonist, Androgen,Receptor Agonists, Androgen
D013997	Time Factors	Elements of limited time intervals, contributing to particular results or situations.	Time Series,Factor, Time,Time Factor
D015735	Mifepristone	A progestational and glucocorticoid hormone antagonist. Its inhibition of progesterone induces bleeding during the luteal phase and in early pregnancy by releasing endogenous prostaglandins from the endometrium or decidua. As a glucocorticoid receptor antagonist, the drug has been used to treat hypercortisolism in patients with nonpituitary CUSHING SYNDROME.	Mifegyne,Mifeprex,Mifégyne,R-38486,R38486,RU-38486,RU-486,ZK-98296,ZK98296,R 38486,RU 38486,RU 486,RU38486,RU486,ZK 98296