BRD9 controls Oxytocin signal pathway in gastric cancer via CACNA2D4 and CALML6

Background: First-line chemotherapeutic agents have great activation treatment in cancers, but the side effect of these kind drugs also hurt the healthy cells, in some cases, cancer cells are induced drug resistance to chemotherapeutic agents. The molecular mechanisms underlying such side effect have been studied in a range of cancer types, yet little is known in depressing the adverse effect of chemotherapeutic drugs by targeting BRD9 in gastric cancers. Methods: We used two gastric cancer cell lines (MGC-803 and AGS) for comparison. We applied molecular and cellular techniques to measure cell survival, mRNA expression, investigated clinical data in the consensus of The Cancer Genome Atlas, and combined with the High-Throughput Sequencing approach in MGC-803 cells and AGS cells, for global gene expression analysis in inhibiting BRD9 conditions. Results: Our studies have shown that cancer cells with BRD9 over-expression, MGC-803 cells, are more sensitive to BRD9 inhibitors, BI9564 or BI7273, than AGS cells. Its mechanism is related to the regulation of CACNA2D4 and CALML6 oncogenes in the Oxytocin signaling pathway. And BRD9 inhibitors can enhance the sensitivity of gastric cancer MGC-803 cells to adriamycin and cisplatin, so we may reduce the dosage of chemotherapeutic agents in curing gastric cancers with BRD9 over-expression by combining BI9564 or BI7273 with adriamycin or cisplatin. Conclusions: Our study elucidates the feasibility and effectiveness of inhibiting BRD9 to reduce the adverse effect of first-line chemotherapeutic agents in treating over-expressed BRD9 gastric cancer, providing a scientific theoretical basis on chemotherapy regimen in over-expressed BRD9 gastric cancer.