Ma Hanwei, Wu Fahong, Bai Yinliang, Wang Tianwei, Ma Shangxian, Guo Liuqing, Liu Guiyuan, Leng Guangxian, Kong Yin, Zhang Youcheng
Laboratory of Hepatic-Biliary-Pancreatic, Department of General Surgery, Lanzhou University Second Hospital, Lanzhou, Gansu, China.
Department of Pediatric Gastroenterology, Lanzhou University Second Hospital, Lanzhou, Gansu, China.
Front Pharmacol. 2022 Oct 13;13:972825. doi: 10.3389/fphar.2022.972825. eCollection 2022.
Licoricidin, a type of isoflavonoid, is extracted from the root of . It has been widely proven that licoricidin possesses multiple biological activities, including anti-cancer effects and a powerful antimicrobial effect against (). However, the exact mechanism of licoricidin against gastric cancer remains unclear. In this study, we comprehensively explored the effects of licoricidin on MGC-803 gastric cancer cells in vitro and in vivo and further elucidated its mechanism of action. Our results revealed that licoricidin exhibited multiple anti-gastric cancer activities, including suppressing proliferation, inducing apoptosis, arresting the cell cycle in G/G phase, and inhibiting the migration and invasion abilities of MGC-803 gastric cancer cells. In addition to this, a total of 5861 proteins were identified by quantitative proteomics research strategy of TMT labeling, of which 19 differential proteins (two upregulated and 17 downregulated) were screened out. Combining bioinformatics analyses and the reported roles in cancer progression of the 19 proteins, we speculated that isoprenyl carboxyl methyltransferase (ICMT) was the most likely target of licoricidin. Western blot assays and IHC assays subsequently proved that licoricidin significantly downregulated the expression of ICMT, both in MGC-803 cells and in xenograft tumors. Moreover, licoricidin effectively reduced the level of active Ras-GTP and blocked the phosphorylation of Raf and Erk, which may be involved in its anti-gastric cancer effects. In summary, we first demonstrated that licoricidin exerted favorable anti-gastric cancer activities the ICMT/Ras pathway, which suggests that licoricidin, as a natural product, could be a novel candidate for the management of gastric cancer.
甘草定，一种异黄酮类化合物，从……的根中提取。已被广泛证明甘草定具有多种生物活性，包括抗癌作用以及对……的强大抗菌作用。然而，甘草定抗胃癌的确切机制仍不清楚。在本研究中，我们全面探究了甘草定在体外和体内对MGC - 803胃癌细胞的作用，并进一步阐明其作用机制。我们的结果显示，甘草定表现出多种抗胃癌活性，包括抑制增殖、诱导凋亡、使细胞周期停滞在G/G期以及抑制MGC - 803胃癌细胞的迁移和侵袭能力。除此之外，通过TMT标记的定量蛋白质组学研究策略共鉴定出5861种蛋白质，其中筛选出19种差异蛋白质（2种上调和17种下调）。结合生物信息学分析以及这19种蛋白质在癌症进展中的报道作用，我们推测异戊烯基羧基甲基转移酶（ICMT）是甘草定最可能的靶点。随后的蛋白质免疫印迹分析和免疫组化分析证明，甘草定在MGC - 803细胞和异种移植肿瘤中均显著下调ICMT的表达。此外，甘草定有效降低了活性Ras - GTP的水平并阻断了Raf和Erk的磷酸化，这可能与其抗胃癌作用有关。总之，我们首次证明甘草定通过ICMT/Ras途径发挥良好的抗胃癌活性，这表明甘草定作为一种天然产物，可能是治疗胃癌的新型候选药物。
