Transferrin dependence of Ga(NO3)3 inhibition of growth in human-derived small cell lung cancer cells

Abstract

The effect of a combination of anti-transferrin receptor (TFR) antibody, 42/6, and Ga(No₃)₃ on cell growth was examined in small cell lung cancer (SCLC) cell lines: classic, NCl-H209, NCl-H345, NCl-H510; and variant, NCl-H82 and NCl-N417. The role of TFR and transferrin(TF) in Ga(No₃)₃ cellular uptake was also tested. Exogenous TF did not enhance the cytotoxicity of Ga. At > 3 μg/mL, Ga(No₃)₃ inhibited growth in all cell lines in TF-supplemented or deficient media. At < 3 μg/mL, Ga stimulated growth for all cells but this effect was eliminated by TF or 42/6. Classic SCLC lines required 3–4-fold less exogenous gallium than variant lines to reduce cell number by 50%. The mean Ga uptake (ng/10⁶ cells) in H345 and H209 cell lines was 4–5-fold compared to H82 and N417 uptake (P < 0.001). 42/6 reduced exogenous TF-stimulated growth. Antibody plus Ga(No₃)₃ caused a slight further cell number decline in all cell lines in TF-supplemented or deficient media. These results suggest that the addition of 42/6 antibody treatment would not increase the effectiveness of Ga(No₃)₃ in patients. Both exogenous and endogenous TF and TFR play an important role in Ga uptake in these cells.