Department of Gastrointestinal Surgery, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong Province, China.
Department of Gastrointestinal Surgery, Binzhou People's Hospital, Binzhou, Shandong Province, China.
J Biochem Mol Toxicol. 2021 May;35(5):e22723. doi: 10.1002/jbt.22723. Epub 2021 Jan 28.
Gastric carcinoma is one of the most aggressive types of cancer that ranks fifth among all cancer incidences and third in cancer mortality. As it exhibits a prolonged asymptomatic condition and high recurrence rate, it is a great challenge to treat gastric cancer. Traditional medicine that utilizes herbal phytochemicals to treat various diseases is a potent alternative for current allopathic treatment. Hence, we evaluated the potency of a phytochemical bilobalide for treating gastric cancer in in vitro and in vivo models. Bilobalide, a sesquiterpenoid, is present in the Ginkgo biloba plant that belongs to the family of Ginkgoaceae. The cytotoxicity effect of bilobalide was evaluated in both gastric cancer (AGS) cells and normal gastric epithelial cells. Apoptosis-inducing property of bilobalide against the AGS cell line was analyzed with different fluorescent staining techniques and terminal deoxynucleotidyl transferase dUTP nick-end labeling assay, and cell cycle analysis was carried out by flow cytometry. The in vivo studies were assessed with N-methyl-N-nitrosourea (MNU)-induced gastric cancer in rats. Serum-specific gastric markers were quantified and histopathological analysis of stomach tissue was performed. The expression of target-signaling molecules was analyzed by a reverse-transcription polymerase chain reaction. The in vitro results proved that bilobalide effectively suppressed the AGS cell growth and induced cell death by nuclear damage and apoptosis induction. The bilobalide treatment effectively arrested the cell cycle of AGS cells via inhibiting the PI3K-signaling pathway. Our in vivo results also confirmed that the bilobalide persuasively inhibited the MNU-induced gastric carcinoma via inhibiting the thioredoxin-fold family proteins and inflammatory markers' expression. Overall, our results authentically prove that bilobalide possesses therapeutic potency to cure gastric carcinoma.
胃癌是最具侵袭性的癌症之一，其发病率在所有癌症中排名第五，死亡率排名第三。由于它表现出较长的无症状期和较高的复发率，因此治疗胃癌是一个巨大的挑战。利用植物化学物质治疗各种疾病的传统医学是替代当前对抗疗法的有力选择。因此，我们评估了植物化学物白果内酯治疗胃癌的体外和体内模型的效力。白果内酯是一种倍半萜烯，存在于银杏科银杏属植物中。在胃癌（AGS）细胞和正常胃上皮细胞中评估了白果内酯的细胞毒性作用。通过不同的荧光染色技术和末端脱氧核苷酸转移酶 dUTP 缺口末端标记测定分析了白果内酯对 AGS 细胞系的诱导凋亡特性，并通过流式细胞术进行了细胞周期分析。通过 N-甲基-N-亚硝基脲（MNU）诱导的大鼠胃癌进行了体内研究。定量了血清特异性胃标志物，并对胃组织进行了组织病理学分析。通过逆转录聚合酶链反应分析了靶信号分子的表达。体外结果证明，白果内酯通过核损伤和凋亡诱导有效地抑制了 AGS 细胞的生长并诱导了细胞死亡。白果内酯处理通过抑制 PI3K 信号通路有效地阻止了 AGS 细胞的细胞周期。我们的体内结果还证实，白果内酯通过抑制硫氧还蛋白折叠家族蛋白和炎症标志物的表达，有效地抑制了 MNU 诱导的胃癌。总的来说，我们的结果确实证明了白果内酯具有治疗胃癌的潜力。
