Crotoxin suppresses the tumorigenic properties and enhances the antitumor activity of Iressa® (gefinitib) in human lung adenocarcinoma SPCA‑1 cells.

Crotoxin (CrTX) is a neurotoxin isolated from the venom of the South American rattlesnake. Previous studies demonstrated that CrTX was able to inhibit the activity of the growth factor receptor tyrosine kinase and that CrTX possesses potent antitumor activity when combined with Iressa, an epidermal growth factor receptor inhibitor. The aim of the present study was to determine the antitumor effect of CrTX and the combination of CrTX with Iressa in lung adenocarcinoma SPCA‑1 cells. The results demonstrated that CrTX inhibited the cellular growth of SPCA‑1 cells via G1 arrest and induction of apoptosis. In addition, the c‑Jun N‑terminal kinase pathway was important in CrTX‑induced apoptosis in SPCA‑1 cells. Notably, CrTX was able to significantly enhance the cytotoxic effects of Iressa in SPCA‑1 cells. The in vivo antitumor assay demonstrated that treatment with either CrTX or Iressa significantly inhibited tumor growth, while the combination of CrTX and Iressa demonstrated the most significant antitumor activity, which was reflected by tumor weight and angiogenesis, presented as microvascular density. Therefore, the present study suggested that CrTX is a potential anti‑lung cancer agent and sensitizer of Iressa.