Published online May 31, 2008.
https://doi.org/10.4111/kju.2008.49.5.392
In vivo Hollow Fiber Assay for Anticancer Drugs' Responsiveness in a Bladder Cancer Model
Abstract
Purpose
The National Cancer Institute (NCI)'s Hollow Fiber Assay (HFA) is currently used as an in vivo screening model to quantitatively define anticancer activity. To investigate the use of HFA in a bladder cancer model, we conducted in vitro and in vivo experiments with several anticancer drugs in nude mice.
Materials and Methods
The human bladder cancer cell lines (CRL2742, 253JP, SW1710, HTB9) were cultured both in vitro and in vivo in polyvinylidene fluoride (PVDF) hollow fibers. The fibers were implanted intraperitoneally (ip) and subcutaneously (sc) into female athymic nude mice (C57BL/6), and the mice were then treated with gemcitabine 120 mg/kg (bolus), cisplatin (3mg/kg), paclitaxel (15mg/kg) or vehicle only (control) for 4-consecutive days. After 6 days, the fibers were retrieved and the viable cell density was analyzed by MTT assay.
Results
The difference between in vitro and in vivo growth was not significant for the CRL2742, 253J-P and SW1710 cell lines; the difference between the ip and sc fibers was also not significant in the CRL2742, SW1710 and HTB9 cell lines. After drug treatment, the percent of growth inhibition revealed constant and effective anticancer activities for the 3 individual drugs.
Conclusions
This study demonstrates the possibility of measuring and quantifying the anticancer effect with using in vivo hollow fiber assay in a bladder cancer model.
Fig. 1
Implanted sc fibers (arrow) in a nude mouse (ip fibers are not shown). sc: subcutaneous, ip: intraperitoneal.
Fig. 2
The differences between in vitro and in vivo (ip+sc) fibers in each of the bladder cancer cell lines. Three of four the cell lines (CRL2742, 253J-P, SW1710) except the HTB9 cell line, reveal no significant differences between the in vitro and in vivo fibers. The difference between the ip and sc fibers was also not significant, except for the 253J-P cell line. ip: intraperitoneal, sc: subcutaneous.
Fig. 3
Percent (%) of growth inhibition (decease of MTT absorbance) after drug (cisplatin, paclitaxel, gemcitabine) injection for each of the cell lines. (A) % growth inhibition for the in vivo (ip+sc) fibers, (B) % growth inhibition for the in ip and sc fibers. ip: intraperitoneal, sc: subcutaneous, Cis: cisplatin, Tax: paclitaxel, Gem: gemcitabine.
Table 1
The MTT absorbance of the in vitro (upper) fibers (18 fibers per each cell line) and the in vivo (lower) intraperitoneal (ip) and subcutaneous (sc) fibers (8 fibers per each cell line)
Table 2
The MTT absorbance after drug exposure (cisplatin 3mg/kg, paclitaxel 15mg/kg or gemcitabine 120mg/kg bolus) at 4-days (1-day for gemcitabine) after intraperitoneal injection. The control group received vehicle (normal saline) injection only. The individual growth inhibition % for each drug (lower)
References
-
Suggitt M, Bibby MC. 50 years of preclinical anticancer drug screening: empirical to target-driven approaches. Clin Cancer Res 2005;11:971–981.
-
-
Alami N, Paterson JS, Belanger S, Grieshaber CK, Leyland-Jones B. In vitro and in vivo activity of C1311 and paclitaxel in three cancer tumor models. AACR Meeting Abstracts 2004;2004:1069–1070.
-
-
Sadar MD, Akopian VA, Beraldi E. Characterization of a new in vivo hollow fiber model for the study of progression of prostate cancer to androgen independence. Mol Cancer Ther 2002;1:629–637.
-
-
Leong CO, Suggitt M, Swaine DJ, Bibby MC, Stevens MF, Bradshaw TD. In vitro, in vivo, and in silico analyses of the antitumor activity of 2-(4-amino-3-methylphenyl)-5-fluorobenzothiazoles. Mol Cancer Ther 2004;3:1565–1575.
-
-
Lee KH, Rhee KH. Correlative effect between in vivo hollow fiber assay and xenografts assay in drug screening. Cancer Res Treat 2005;37:190–200.
-
-
Wells RS, Campbell EW, Swartzendruber DE, Holland LM, Kraemer PM. Role of anchorage in the expression of tumorigenicity of untransformed mouse cell lines. J Natl Cancer Inst 1982;69:415–423.
-
-
Gorelik E, Ovejera A, Shoemaker R, Jarvis A, Alley M, Duff R, et al. Microencapsulated tumor assay: new short-term assay for in vivo evaluation of the effects of anticancer drugs on human tumor cell lines. Cancer Res 1987;47:5739–5747.
-
-
Peters GJ, Bergman AM, Ruiz van Haperen VW, Veerman G, Kuiper CM, Braakhuis BJ. Interaction between cisplatin and gemcitabine in vitro and in vivo. Semin Oncol 1995;22 4 Suppl 11:72–79.
-
-
Shipley LA, Brown TJ, Cornpropst JD, Hamilton M, Daniels WD, Culp HW. Metabolism and disposition of gemcitabine, and oncolytic deoxycytidine analog, in mice, rats, and dogs. Drug Metab Dispos 1992;20:849–855.
-
-
Braakhuis BJ, Ruiz van Haperen VW, Boven E, Veerman G, Peters GJ. Schedule-dependent antitumor effect of gemcitabine in in vivo model system. Semin Oncol 1995;22 4 Suppl 11:42–46.
-
-
Phillips RM, Pearce J, Loadman PM, Bibby MC, Cooper PA, Swaine DJ, et al. Angiogenesis in the hollow fiber tumor model influences drug delivery to tumor cells: implications for anticancer drug screening programs. Cancer Res 1998;58:5263–5266.
-
-
Shnyder SD, Cooper PA, Scally AJ, Bibby MC. Reducing the cost of screening novel agents using the hollow fibre assay. Anticancer Res 2006;26:2049–2052.
-