Abstract
The effects of a bombesin/gastrin releasing peptide (BB/GRP) receptor antagonist, PD176252, and histone deacetylase (HDAC) inhibitor, MS-275, were investigated on human lung cancer cell lines. Using the MTT assay, PD176252 and MS-275 inhibited the proliferation of NCI-H1299 cells with IC50 values of 7 and 5 μg/mL, respectively. Using MS-275 and PD176252 together, the ability to inhibit lung cancer cellular growth increased significantly. The combination index for MS-275 and PD176252 was < 0.2, indicating that the compounds are highly synergistic in inhibiting lung cancer cellular growth. Also, MS-275 and PD 176252 together strongly inhibited the clonal growth of NCI-H345 or NCI-H1299 cells. MS-275 had little effect on the expression of lung cancer cellular GRP or GRP receptors, but increased expression of transforming growth factor-β receptor II (TGF-β RII). These results indicate that GRP receptor antagonists may potentiate the action of histone deacetylase inhibitors on lung cancer cellular proliferation by increasing expression of tumor suppressor genes.
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Moody, T.W., Nakagawa, T., Kang, Y. et al. Bombesin/gastrin-releasing peptide receptor antagonists increase the ability of histone deacetylase inhibitors to reduce lung cancer proliferation. J Mol Neurosci 28, 231–238 (2006). https://doi.org/10.1385/JMN:28:3:231
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DOI: https://doi.org/10.1385/JMN:28:3:231