Purpose: To determine the sensitivity of lung cancer cell lines to different combinations of BET and HDAC inhibitors and to inquire possible associations with the genetic and molecular profiles.

Methods: A panel of lung cancer cell lines were treated in vitro with BET and HDAC inhibitors. The capability of each compound, administered individually or in combination (IC50), to inhibit cell proliferation was assessed by MTT assays. Drug interaction analysis was performed using Compusyn software. The protein and gene expression levels were determined using western blot and real time PCR, respectively.

Results: We found that about 70% of the cell lines tested were sensitive to BET inhibitors and about 60% responded to HDAC inhibitors. In both cases, increased sensitivity was accompanied by changes in cell morphology, a reduction of the MYC protein levels and an increase in the levels of apoptotic-related markers. We also determined the effects of the combination of these epigenetic treatments in cell growth. Our results showed a synergic effect in about 75% of the cell lines which was also correlated with dramatic changes in cell morphology, in apoptosis and in decreasing the levels of the MYC protein. Finally, we determined the possible correlation of the sensitivity to these epigenetic drugs and the expression levels of some genes implicated in lung carcinogenesis.

Conclusions: Our data showed that lung cancer cells responded to BET and HDAC inhibitors and that the combination of both drugs has a synergistic effect in cell growth inhibition, suggesting that this could be an effective treatment in lung cancer. Our data also point out to certain genes as potential biomarkers to determine sensitivity to these compounds.

Citation Format: Sara Verdura, Manuel Torres-Diz, Montserrat Sanchez-Cespedes. Determination of sensitivity to BET and HDAC inhibitors in lung cancer cell lines [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 5073. doi:10.1158/1538-7445.AM2017-5073