Combined Treatment of Cisplatin With Caffeic Acid Phenethyl Ester Demonstrates Additive Growth Inhibition on Non-small Cell Lung Cancer Cells

Background/Aim: Non-small cell lung cancer (NSCLC) accounts for approximately 85% of all lung cancer cases. While cisplatin remains standard treatment for NSCLC, development of drug resistance causes failure of treatment. Caffeic acid phenethyl ester (CAPE) has been reported to cause synergistic inhibitory effects with cisplatin in other cancer types. In this study, we investigated whether combination of cisplatin with CAPE enhances the suppression of NSCLC cell proliferation and survival.

Materials and Methods: Proliferation assays, MTT assays, and flow cytometry were performed to examine the effects of cisplatin, CAPE and combined treatment on survival and cell cycle of NSCLC cells. Micro-Western Array (MWA) was used to explore the signaling proteins being affected by cisplatin, CAPE or combined treatment.

Results: Both agents independently reduced the viability of H1299 and A549 cells in a dose-dependent manner. Combined treatment of cisplatin with CAPE exerted additive suppressive effect compared to cisplatin alone, and the suppressive effects accumulated over time. Flow cytometry analysis revealed that both cisplatin alone and the combination treatment induced G₂-M phase cell cycle arrest. Furthermore, MWA analysis showed that the combination treatment repressed the expression of proteins involved in PI3K-AKT signaling and cell cycle progression.

Conclusion: Combined treatment of cisplatin with CAPE may reduce the required dose of cisplatin for growth inhibition of NSCLC cells and delay or prevent the development of drug resistance in NSCLC.