Oxymatrine induces apoptosis in non-small cell lung cancer cells by downregulating TRIM46

Sophora flavescens Aiton, a traditional Chinese medicine that was supposed to predominantly play an anti-inflammatory role, has been used to treat multiple diseases, including cancer, for over two thousand years. Recently, it has attracted increasing attention due to the anti-tumor properties of Oxymatrine, one of the most active alkaloids extracted from S. flavescens. This study aims to explore it's anti-tumor effects in non-small cell lung cancer (NSCLC) and the underlying mechanisms. We first investigated the effects of oxymatrine on cell apoptosis in lung cancer cell lines A549 and PC9 as well as explored related genes in regulating the apoptosis by transcriptome analysis. Subsequently, to further study the role of TRIM46, we constructed two types of TRIM46 over-expression cells (A549^TRIM46+ and PC9^TRIM46+ cells) and then investigated the effect of TRIM46 on oxymatrine-induced apoptosis. Moreover, we explored the effect of TRIM46 on downstream signaling pathways. Transcriptome analysis suggested that shared differentially expressed genes (DEGs) in A549 and PC9 cells treated with oxymatrine were CACNA1I, PADI2, and TRIM46. According to TCGA database analysis, the abundance of TRIM46 expression was higher than CACNA1I, and PADI2 in lung cancer tissues, then was selected as the final DEG for subsequent studies. We observed that oxymatrine resulted in down-expression of TRIM46 as well as induced the apoptosis of the cancer cells in a dose- and time-dependent manner. Meanwhile, we found that apoptosis induced by oxymatrine was inhibited by over-expressing TRIM46. Furthermore, our study indicated that the NF-κB signaling pathway was involved in apoptosis suppressed by TRIM46. We conclude that TRIM46 is the direct target of oxymatrine to induce anti-tumor apoptosis and may activate the downstream NF-κB signaling pathway.