Synergistic effects of piperlongumine and gemcitabine against KRAS mutant lung cancer

Objective: To determine the combined efficacy of piperlongumine and gemcitabine for treatment of KRAS mutant lung cancer. Methods: The cell growth inhibition of piperlongumine, gemcitabine, and piperlongumine plus gemcitabine was measured by Cell Counting Kit‑8 assay and the combination index was calculated. In addition, the combined effects of piperlongumine and gemcitabine on cell apoptosis, reactive oxygen species (ROS) contents, and microtubule-associated protein 1 light chain 3B (LC3B) expression were examined. Results: Piperlongumine increased ROS contents and LC3B-II expression. Following the combined treatment with piperlongumine and 10 mM N-acetyl-L-cysteine (NAC), intracellular ROS and cell viability returned to normal levels, and the expression of LC3B-II decreased to the predose level. Gemcitabine also induced cell apoptosis, increased ROS contents, and LC3B-II expression. The combination of piperlongumine with gemcitabine exhibited a synergetic anticancer activity with the combination index <1. The combined application of gemcitabine and piperlongumine yielded synergistic effects on cell apoptosis, but failed to synergistically increase ROS levels and LC3B-II expression. Conclusion: Combination therapy with piperlongumine and gemcitabine is a promising treatment option for KRAS mutant lung cancer.