Synergistic effects of pemetrexed and amrubicin in non-small cell lung cancer cell lines: Potential for combination therapy

• The combination of PEM/AMR has a synergistic effect in several NSCLC cell lines.
• AMRol reduced TS expression in a dose-dependent manner in every cell lines.
• AMRol also increased the proportion of cells in S phase at the effective dose.
• AMR plays an important role in the synergism between two agents.

The purpose is to examine the synergistic effect of pemetrexed (PEM) and amrubicin (AMR) on the proliferation of lung cancer cell lines. In vitro, dose-dependent synergistic effects of concurrent PEM and AMRol, which is an active metabolite of AMR were observed in A549 and H460 cells. In real-time RT-qPCR analysis and western blotting, expression of the target enzymes of PEM were suppressed in cells treated with amrubicinol alone. In vivo, AMR/PEM treatment also showed synergistic antitumor activity both in A549-bearing and H520-bearing mice. PEM and AMR work synergistically to inhibit the proliferation of several different lung cancer cell lines.