Squamous cell cancer cell lines: sensitivity to bleomycin and suitability for animal xenograft studies.
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.
Jääskelä-Saari
H A
HA
Department of Otorhinolaryngology, Helsinki University Central Hospital, Finland.
Kairemo
K J
KJ
Ramsay
H A
HA
Grénman
R
R
D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000627:therapeutic use*; D001761:Bleomycin / Q000031:analogs & derivatives* / Q000627:therapeutic use; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy* / Q000532:radiotherapy; D003131:Combined Modality Therapy / Q000379:methods; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D007205:Indium Radioisotopes / Q000627:therapeutic use*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D009942:Organometallic Compounds / Q000627:therapeutic use*; D014183:Transplantation, Heterologous; D014407:Tumor Cells, Cultured
D000903:Antibiotics, Antineoplastic; D007205:Indium Radioisotopes; D009942:Organometallic Compounds; C047120:indium-bleomycin; D001761:Bleomycin