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 β-emitting radionuclide combined to bleomycin (In-III-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-III-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.

Key Words:

• squamous cell cancer
• bleomycin
• tumor xenograft
• head and neck neoplasms