GROWTH AND CHEMOTHERAPEUTIC RESPONSE OF CELLS IN A HOLLOW-FIBER IN-VITRO SOLID TUMOR-MODEL

被引:65
作者
CASCIARI, JJ
HOLLINGSHEAD, MG
ALLEY, MC
MAYO, JG
MALSPEIS, L
MIYAUCHI, S
GREVER, MR
WEINSTEIN, JN
机构
[1] NCI,DIV CANC TREATMENT,DEV THERAPEUT PROGRAM,BETHESDA,MD 20892
[2] NCI,FREDERICK CANC RES & DEV CTR,DIV CANC TREATMENT,DEV THERAPEUT PROGRAM,FREDERICK,MD 21702
[3] HOKKAIDO UNIV,FAC PHARMACEUT SCI,DEPT BIOPHYS CHEM,SAPPORO,HOKKAIDO 060,JAPAN
关键词
D O I
10.1093/jnci/86.24.1846
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Background: Cancer treatments that appear promising in tissue culture are often less effective in solid tumors, in part because of the proliferative and microenvironmental heterogeneity that develops in these tumors as they grow. Heterogeneous tumor models are thus needed for drug screening. Purpose: Our goal was to develop and test for drug evaluation a solid tumor model based on cell growth inside biocompatible hollow fibers. Methods: Building on the experience of Hollingshead and co-workers with a sparse-cell, hollow-fiber tumor model, we tested six human tumor cell lines for in vitro growth inside 450-mu m internal-diameter polyvinylidine fluoride fibers and examined them histologically. Human SW620 colon carcinoma cells grown in hollow fibers were also examined using electron microscopy, and their doxorubicin sensitivity was assessed. A colorimetric assay based on sulforhodamine B was adopted to replace the more cumbersome clonogenic cell survival assay. Results: Five of the human tumor cell lines tested grew to confluence, forming heterogeneous in vitro tumors with subpopulations of viable and necrotic cells. For SW620 hollow-fiber tumors, maximum viable cell populations in excess of 10(8) cells/ml were obtained after 8 days of growth. This viable cell density remained roughly constant for 3-4 days, permitting dose-response experiments over this time interval. Tumor cells in hollow fibers were much more resistant to a 4-hour doxorubicin exposure than were tumor cells in monolayers: LC(50) values (i.e., the drug concentrations at which the plating efficiency equals one-half the plating efficiency of untreated cells) of 3.5 mu M and 0.16 mu M were obtained for hollow-fiber tumors and monolayers, respectively. LC(50) values decreased when drug exposure time was increased. Results from the colorimetric assay were in agreement with those from the clonogenic assay. Conclusion: The successful growth of tumor cells to confluence in hollow fibers and the feasibility of performing in vitro drug dose-response experiments with a relatively easy colorimetric assay demonstrate the potential of the hollow-fiber solid tumor model as a tool for experimental therapeutic research. Implication: Hollow-fiber solid tumors may prove useful for experimental drug evaluation.
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页码:1846 / 1852
页数:7
相关论文
共 29 条
[1]  
ACKER H, 1987, CANCER RES, V47, P3504
[2]   EFFECT OF HYPOXIA ON GROWTH AND RADIATION RESPONSE OF MAMMALIAN-CELLS IN CULTURE [J].
BEDFORD, JS ;
MITCHELL, JB .
BRITISH JOURNAL OF RADIOLOGY, 1974, 47 (562) :687-696
[3]  
Boyd M.K., 1989, CANCER PRINCIPLES PR, V3, P1
[4]   MATHEMATICAL-MODELING OF MICROENVIRONMENT AND GROWTH IN EMT6/RO MULTICELLULAR TUMOR SPHEROIDS [J].
CASCIARI, JJ ;
SOTIRCHOS, SV ;
SUTHERLAND, RM .
CELL PROLIFERATION, 1992, 25 (01) :1-22
[5]   VARIATIONS IN TUMOR-CELL GROWTH-RATES AND METABOLISM WITH OXYGEN CONCENTRATION, GLUCOSE-CONCENTRATION, AND EXTRACELLULAR PH [J].
CASCIARI, JJ ;
SOTIRCHOS, SV ;
SUTHERLAND, RM .
JOURNAL OF CELLULAR PHYSIOLOGY, 1992, 151 (02) :386-394
[7]   DISTRIBUTION AND ACTIVITY OF ANTINEOPLASTIC DRUGS IN A TUMOR-MODEL [J].
DURAND, RE .
JNCI-JOURNAL OF THE NATIONAL CANCER INSTITUTE, 1989, 81 (02) :146-152
[8]  
FREYER JP, 1986, CANCER RES, V46, P3153
[9]   DNA-CONTAINING LIPOSOMES AS A MODEL FOR THE STUDY OF CELL-MEMBRANE PERMEATION BY ANTHRACYCLINE DERIVATIVES [J].
FREZARD, F ;
GARNIERSUILLEROT, A .
BIOCHEMISTRY, 1991, 30 (20) :5038-5043
[10]  
GORELIK E, 1987, CANCER RES, V47, P5739