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JQ 1 and PI 3K inhibition synergistically reduce salivary adenoid cystic carcinoma malignancy by targeting the c‐Myc and EGFR signaling pathways
Author(s) -
Liu Xiaojing,
Wu Haitao,
Huang Ping,
Zhang Fenghe
Publication year - 2019
Publication title -
journal of oral pathology and medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.887
H-Index - 83
eISSN - 1600-0714
pISSN - 0904-2512
DOI - 10.1111/jop.12784
Subject(s) - gene knockdown , cancer research , flow cytometry , apoptosis , western blot , cell culture , biology , signal transduction , microbiology and biotechnology , chemistry , biochemistry , gene , genetics
Background To investigate the therapeutic mechanism of the BRD 4 inhibitor JQ 1 in SACC ‐83 cells and explore strategies to enhance its therapeutic potential. Material and Methods SACC ‐83 cells were used in the experiment. Immunohistochemistry was used to assess BRD 4 expression in SACC tissues and corresponding adjacent non‐tumor tissues. Cell viability and proliferation were evaluated using the Cell Counting Kit‐8 assay. Flow cytometry was used to quantitate apoptosis. Levels of cleaved caspase‐3, BRD 4, c‐Myc, pEGFR (γ‐1173), and EGFR were determined by quantitative real‐time PCR and Western blot. To study the role of EGFR in JQ 1 resistance, we generated EGFR knockdown SACC ‐83 cells by si RNA transfection. Results Our study revealed that BRD 4 was overexpressed and could be a treatment target in SACC . The BRD 4 inhibitor JQ 1 markedly inhibited c‐Myc expression in SACC ‐83 cells, which produced modest therapeutic effects. Nevertheless, the EGFR pathway was strongly activated following JQ 1 treatment, which led to JQ 1 resistance. Combined JQ 1 and PI 3K inhibitor treatment effectively increased the therapeutic potential by inhibiting the EGFR and c‐Myc signaling pathways in SACC ‐83 cells. Moreover, EGFR knockdown sensitized SACC ‐83 cells to JQ 1. Conclusion These data demonstrate that EGFR and c‐Myc signaling synergistically drive SACC progression. The JQ 1 and PI 3K inhibitor combination exhibited a strong synergistic effect by suppressing c‐Myc and EGFR in SACC ‐83 cells, identifying a novel rational combinatorial treatment. Moreover, EGFR expression influences the sensitivity of SACC ‐83 cells to JQ 1, which is useful for planning treatment.