Transferrin dependence of Ga(NO 3 ) 3 inhibition of growth in human‐derived small cell lung cancer cells

The effect of a combination of anti‐transferrin receptor (TFR) antibody, 42/6, and Ga(No 3 ) 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(No 3 ) 3 cellular uptake was also tested. Exogenous TF did not enhance the cytotoxicity of Ga. At > 3 μg/mL, Ga(No 3 ) 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/10 6 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(No 3 ) 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(No 3 ) 3 in patients. Both exogenous and endogenous TF and TFR play an important role in Ga uptake in these cells. © 1996 Wiley‐Liss, Inc.