Home Blog of Signal Transduction Epigenetics Epigenetic Reader Domain Inhibition of BRD4 enhanced the tumor suppression effect of dasatinib in gastric cancer

Category

Archives

Popular Post

ESKM, a novel therapeutic agent for sensitive and resistant PH+ leukemias

The mechanism of resistance to JAK2 inhibitor in myeloproliferative neoplasms patients

Effects of PARP inhibitors in BRCA gene-mutated ovarian cancer

DASATINIB; An inhibitor of Receptor Tyrosine Kinase

GP130/JAK/STAT3 signaling pathway induces multiple myeloma

Inhibition of BRD4 enhanced the tumor suppression effect of dasatinib in gastric cancer

BRD4, a member of the bromodomain and extraterminal (BET) family, is elevated in multiple cancer tissues, including gastric cancer (GC). Targeted therapy with BRD4 may help improve the overall survival of patients with GC. Meanwhile, the approved multi-target kinase inhibitor, dasatinib, was recently reported to show varied tumor-suppressive effects in GC cells. This study investigated BRD4 expression in vivo and in vitro using immunohistochemistry and western blotting, respectively. We discussed the relationship between BRD4 expression and patient prognosis. Next, the antitumor efficacy of dasatinib was measured in BRD4-knockdown GC cells to determine the role of BRD4 blockage in dasatinib treatment. Finally, molibresib, a BET inhibitor, was used to measure the cooperative function of BRD4 inhibition and dasatinib treatment in three GC cell lines. Epithelial BRD4 expression was higher in tumoral and metastatic tissues and was strongly associated with unfavorable tumor, node, and metastasis stages and survival. BRD4 expression was heterogeneous in the three GC cell lines tested in vitro. In SGC7901, a BRD4-high GC cell line, knockdown of BRD4 using specific siRNAs suppressed cell growth individually and cooperatively with dasatinib. Moreover, molibresib and dasatinib showed a cooperative effect in suppressing the proliferation of BRD4-high GC cells. In conclusion, we confirmed that increased epithelial BRD4 expression is associated with poor disease stage and prognosis in GC and BRD4 blockage might be a valuable strategy to improve the sensitivity of dasatinib and other drugs in the chemotherapy of advanced GC.

 

Comments：

The study investigated the potential of targeting BRD4, a member of the BET family, in gastric cancer (GC) to improve patient prognosis. The study found that BRD4 expression was elevated in tumoral and metastatic tissues and was strongly associated with unfavorable tumor, node, and metastasis stages and survival. The study further found that knockdown of BRD4 using specific siRNAs suppressed cell growth individually and cooperatively with dasatinib, a multi-target kinase inhibitor with varied tumor-suppressive effects in GC cells. The study also demonstrated that the BET inhibitor, molibresib, showed a cooperative effect with dasatinib in suppressing the proliferation of BRD4-high GC cells.

Overall, the study suggests that BRD4 blockage might be a valuable strategy to improve the sensitivity of dasatinib and other drugs in the chemotherapy of advanced GC. The study highlights the importance of identifying and targeting specific molecular pathways to improve cancer treatment outcomes.

Related Products

Cat.No. Product Name Information
S7189 Molibresib (I-BET-762) Molibresib (I-BET-762, GSK525762, GSK525762A) is an inhibitor for BET proteins with IC50 of ~35 nM in a cell-free assay, suppresses the production of proinflammatory proteins by macrophages and blocks acute inflammation, highly selective over other bromodomain-containing proteins.

Related Targets

Epigenetic Reader Domain