Squamous cell cancer cell lines: sensitivity to bleomycin and suitability for animal xenograft studies.

Abstract

Bleomycin (BLM) is a natural antibiotic, toxic to dividing cells (G2/M-phase), also proven effective in squamous cell carcinomas (SCC). We have clinically shown that a short-range beta-emitting radionuclide combined to bleomycin (In-111-BLMC) is a tumor-targeting agent in SCCs. With higher radionuclide activities it may be possible to develop a more effective agent, to be tested in animal studies. Using a 96-well clonogenic assay we investigated three SCC cell lines, grown in our own laboratory. IC20, IC50 and IC90 values for BLM were determined. The UT-SCC-12A and UT-SCC-12B cells were originated from a primary tumor and a metastasis of the same patient. UT-SCC-12A cells were also inoculated subcutaneously into nude mice and the tumor growth was analysed. The IC50 value for UT-SCC-19A cell line was 4.0 +/- 1.3 nM. UT-SCC-12A and UT-SCC-12B were both more resistant to BLM; IC50 values were 14.2 +/- 2.8 nM and 13.0 +/- 1.1 nM, respectively. Within 35 days the weight of nude mice increased 2.8 +/- 0.6g. At 25 and 35 days after tumor inoculations the tumor volumes were 111 +/- 51 mm3 and 874 +/- 577 mm3, respectively. The calculated doubling time was 3.86 +/- 0.76 days. SCC cell lines demonstrate different sensitivity to BLM. Our SCC tumor xenograft model showed a rapid growth proper for radiochemotherapeutic studies using In-111-BLMC. The uptake of In-111-BLMC in vivo has been directly proportional to proliferation activity, and the tumors with high binding capacity could be predicted from animal model dose calculations.

• Authors: H A Jääskelä-Saari, K J Kairemo, H A Ramsay, R Grénman
• Journal: Acta oto-laryngologica. Supplementum (Acta Otolaryngol Suppl) Vol. 529 Pg. 241-4 ( 1997) ISSN: 0365-5237 [Print] Norway
• PMID: 9288321 (Publication Type: Journal Article)

Chemical References

• Antibiotics, Antineoplastic
• Indium Radioisotopes
• Organometallic Compounds
• indium-bleomycin
• Bleomycin

Topics

• Animals
• Antibiotics, Antineoplastic (therapeutic use)
• Bleomycin (analogs & derivatives, therapeutic use)
• Carcinoma, Squamous Cell (drug therapy, radiotherapy)
• Combined Modality Therapy (methods)
• Drug Screening Assays, Antitumor
• Humans
• Indium Radioisotopes (therapeutic use)
• Male
• Mice
• Mice, Inbred BALB C
• Mice, Nude
• Neoplasm Transplantation
• Organometallic Compounds (therapeutic use)
• Transplantation, Heterologous
• Tumor Cells, Cultured