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eIF4F Inhibition Sensitizes Non‐Small Cell Lung Cancer Cells to a Topoisomerase II Inhibitor

Lung cancer is one of the most common and deadly cancers worldwide. In the past, Etoposide (ETP), a topoisomerase II inhibitor, has been used to treat non‐small cell lung cancer (NSCLC). However, high concentrations of ETP have been shown to have considerable adverse effects. Combining ETP with another drug as a chemosensitizer could increase the efficacy of ETP. Combination therapies with ETP have been largely unexplored. In past studies, NSCLC has been treated with a novel drug compound, 4EGI‐1, a translation inhibitor. By chemosensitizing NSCLC with 4EGI‐1, we hypothesized that we could decrease the amount of ETP needed for effective treatment. Here we examine the relationship between different concentrations of ETP and 4EGI‐1 and their effect on lung cancer cells. Cell death was used as an assay to determine the efficacy of the agents separately and in combination. The combined effects of ETP and 4EGI‐1 on NSCLC were observed to reduce cell viability by 76‐84%, a significant increase from using no treatment, or using either drug alone. ETP alone reduced cell viability by 52%, and 4EGI‐1 alone reduced cell viability by 52‐64%. From the data, we can conclude that combining ETP and 4EGI‐1 compared to using either drug alone led to significantly lower cell viability (Student's T‐test, p < 0.02). This in vitro study demonstrates the improved activity of ETP with the addition of the translation inhibitor 4EGI‐1.