Kim Won-Jin, Kim Woong, Bae Jang-Mi, Gim Jungsoo, Kim Seok-Jun
Department of Integrative Biological Sciences, Chosun University, Gwangju 61452, Korea.
BK21 FOUR Educational Research Group for Age-Associated Disorder Control Technology, Chosun University, Gwangju 61452, Korea.
Plants (Basel). 2021 May 22;10(6):1047. doi: 10.3390/plants10061047.
Gastric cancer is a malignant tumor with a high incidence and mortality rate worldwide. Nevertheless, anticancer drugs that can be used for gastric cancer treatment are limited. Therefore, it is important to develop targeted anticancer drugs for the treatment of gastric cancer. Dehydroabietic acid (DAA) is a diterpene found in tree pine. Previous studies have demonstrated that DAA inhibits gastric cancer cell proliferation by inducing apoptosis. However, we did not know how DAA inhibits the proliferation of gastric cancer cells through apoptosis. In this study, we attempted to identify the genes that induce cell cycle arrest and cell death, as well as those which are altered by DAA treatment. DAA-regulated genes were screened using RNA-Seq and differentially expressed genes (DEGs) analysis in AGS cells. RNA-Seq analysis revealed that the expression of survivin, an apoptosis inhibitor, was significantly reduced by DAA treatment. We also confirmed that DAA decreased survivin expression by RT-PCR and Western blotting analysis. In addition, the ability of DAA to inhibit survivin was compared to that of YM-155, a known survivin inhibitor. DAA was found to have a stronger inhibitory effect in comparison with YM-155. DAA also caused an increase in cleaved caspase-3, an apoptosis-activating protein. In conclusion, DAA is a potential anticancer agent for gastric cancer that inhibits survivin expression.
胃癌是一种在全球范围内发病率和死亡率都很高的恶性肿瘤。然而，可用于治疗胃癌的抗癌药物有限。因此，开发用于治疗胃癌的靶向抗癌药物很重要。脱氢枞酸（DAA）是一种在松树中发现的二萜类化合物。先前的研究表明，DAA通过诱导凋亡来抑制胃癌细胞增殖。然而，我们并不清楚DAA如何通过凋亡抑制胃癌细胞的增殖。在本研究中，我们试图鉴定诱导细胞周期停滞和细胞死亡的基因，以及那些因DAA处理而发生改变的基因。在AGS细胞中，使用RNA测序（RNA-Seq）和差异表达基因（DEG）分析筛选DAA调控的基因。RNA-Seq分析显示，凋亡抑制因子survivin的表达在DAA处理后显著降低。我们还通过逆转录聚合酶链反应（RT-PCR）和蛋白质免疫印迹分析证实DAA降低了survivin的表达。此外，将DAA抑制survivin的能力与已知的survivin抑制剂YM-155进行了比较。结果发现，与YM-155相比，DAA具有更强的抑制作用。DAA还导致凋亡激活蛋白——裂解的半胱天冬酶-3增加。总之，DAA是一种潜在的胃癌抗癌药物，可抑制survivin表达。
