Gleevec (STI-571) inhibits lung cancer cell growth (A549) and potentiates the cisplatin effect in vitro

Peilin Zhang¹ , Wei Yi Gao¹ , Steven Turner² and Barbara S Ducatman¹

¹Department of Pathology & Cancer Center, West Virginia University Robert C. Byrd Health Sciences Center, Morgantown, WV 26506-9203 USA

²Protea Biosciences. Inc. P.O box 9203 Morgantown, WV 26506-9203 USA

author email corresponding author email

Molecular Cancer 2003, 2:1doi:10.1186/1476-4598-2-1


Published:	3 January 2003

Abstract

Background

Gleevec (aka STI571, Imatinib) is a recently FDA approved anti-tumor drug for chronic myelogenous leukemia. Gleevec binds specifically to BCR-ABL tyrosine kinase and inhibit the tyrosine kinase activity. It cross-reacts with another two important membrane tyrosine kinase receptors, c-kit and PDGF receptors. We sought to investigate if Gleevec has a potential role in treatment of non-small cell lung cancer.

Results

We have shown that Gleevec alone can inhibit the A549 lung cancer cell growth in dose-dependent manner, and the optimal concentration of Gleevec inhibition of A549 cell growth is at the range of 2–3 μM (IC50). We have also shown that A549 cells are resistant to cisplatin treatment (IC50 64 μM). Addition of Gleevec to the A549 cells treated with cisplatin resulted in a synergistic cell killing effect, suggesting that Gleevec can potentiate the effect of cisplatin on A549 cells. We also showed that the A549 lung cancer cells expresses the platelet derived growth factor receptor α, and the inhibitory effects of Gleevec on A549 cells is likely mediated through inhibition of PDGFR α phosphorylation. We further tested 33 lung cancer patients' tumor specimens to see the frequency of PDGFR-α expression by tissue micro-arrays and immunohistochemistry. We found that 16 of the 18 squamous carcinomas (89%), 11 of the 11 adenocarcinomas (100%), and 4 of the 4 small cell lung cancers (100%) expressed PDGFR-α.

Conclusion

These results suggest a potential role of Gleevec as adjuvant therapeutic agent for treatment of non-small cell lung cancer.