A Novel Multi-Target Tyrosine Kinase Inhibitor Anlotinib Combined With Irinotecan Has In-Vitro Anti-Tumor Activity Against Human Small-Cell Lung Cancer

Anlotinib is a multi-target tyrosine kinase inhibitor developed independently in China. Its biological effects remain unclear in small-cell lung cancer (SCLC). The current study aimed to evaluate the effects of anlotinib in combination with irinotecan on H446 and H2227 SCLC cell lines and provide new treatment strategy for SCLC. Cell growth of two cell lines was inhibited by anlotinib, irinotecan and the combination in a dose-dependent manner. After 72 h incubation, the inhibition rate was greater in the combination group than all single drug group. A similar result was found when apoptosis was assessed after 12 h, but not after 6 h of treatment. Compared with single drug, combination drug suppressed the migration and invasion abilities in two cell lines; however, there was no difference between individual anlotinib or irinotecan. The colony formation rate was obviously lower in the combination group. Vascular endothelial growth factor receptor, fibroblast growth factor receptor (FGFR) and platelet-derived growth factor receptor were expressed in two cell lines after treatment regardless single or combination, but FGFR was expressed more after combination treatment than anlotinib. The expression of phosphorylated (p) ERK was decreased with anlotinib alone or combination treatment and pAKT expression was impaired with combination treatment, but not with anlotinib or irinotecan alone. The biological function of anlotinib and irinotecan may be mediated through the AKT/ERK signaling pathway. Additional investigations on biomarker-guided patient-stratification and elucidating individualized targets in patients anlotinib are urgently needed.