Li Lin, Dong Zhen, Shi Pengfei, Tan Li, Xu Jie, Huang Pan, Wang Zhongze, Cui Hongjuan, Yang Liqun
State Key Laboratory of Silkworm Genome Biology, Institute of Sericulture and Systems Biology, College of Sericulture and Textile and Biomass Science, Southwest University, Chongqing, China.
Department of Immunology, School of Basic Medicine, Southwest Medical University, Luzhou, China.
Front Pharmacol. 2020 Nov 24;11:584960. doi: 10.3389/fphar.2020.584960. eCollection 2020.
Gastric cancer is one of the most common malignant tumors. Bruceine D (BD) is one of the extracts of . In recent years, it has been reported that BD has anti-tumor activity in some human cancers through different mechanisms. Here, this study try to explore the effect of BD on gastric cancer and its regulatory mechanism. Cell proliferation ability was detected by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assays, 5-bromo-2-deoxyuridine (BrdU) staining and soft agar colony formation assay, respectively. The tumor xenograft model was used to verify the effect of BD on the tumorigenicity of gastric cancer cells . Flow cytometry analysis and Western blot assay were performed to detect cell cycle and apoptosis. Gastric cancer cells were analyzed by transcriptome sequencing. The interaction between LINC01667, microRNA-138-5p (miR-138-5p) and Cyclin E1 was verified by dual luciferase experiment and RT-PCR assays. We found that BD significantly inhibited cell proliferation and induced cell cycle arrest at S phase in gastric cancer cells. Transcriptome analysis found that the expression of a long non-coding RNA, LINC01667, were significantly down-regulated after BD treatment. Mechanically, it was discovered that LINC01667 upregulated the expression of Cyclin E1 by sponging miR-138-5p. Furthermore, BD enhanced the chemosensitivity of gastric cancer cells to doxorubicin, a clinically used anti-cancer agent. BD inhibit the growth of gastric cancer cells by downregulating the LINC01667/miR-138-5p/Cyclin E1 axis. In addition, BD enhances the chemosensitivity of gastric cancer cells to doxorubicin. This study indicates that BD may be used as a candidate drug for the treatment of patients with gastric cancer.
胃癌是最常见的恶性肿瘤之一。鸦胆子素D（BD）是[植物名称缺失]的提取物之一。近年来，有报道称BD通过不同机制在某些人类癌症中具有抗肿瘤活性。在此，本研究试图探讨BD对胃癌的影响及其调控机制。分别通过3-(4,5-二甲基噻唑-2-基)-2,5-二苯基四氮唑溴盐（MTT）法、5-溴-2'-脱氧尿苷（BrdU）染色和软琼脂集落形成试验检测细胞增殖能力。利用肿瘤异种移植模型验证BD对胃癌细胞致瘤性的影响。进行流式细胞术分析和蛋白质免疫印迹试验以检测细胞周期和凋亡。通过转录组测序分析胃癌细胞。通过双荧光素酶实验和逆转录-聚合酶链反应（RT-PCR）试验验证长链非编码RNA LINC01667、微小RNA-138-5p（miR-138-5p）和细胞周期蛋白E1之间的相互作用。我们发现BD显著抑制胃癌细胞的增殖并诱导细胞周期停滞于S期。转录组分析发现，BD处理后一种长链非编码RNA LINC01667的表达显著下调。机制上，发现LINC01667通过海绵吸附miR-138-5p上调细胞周期蛋白E1的表达。此外，BD增强了胃癌细胞对临床上使用的抗癌药物阿霉素的化学敏感性。BD通过下调LINC01667/miR-138-5p/细胞周期蛋白E1轴抑制胃癌细胞的生长。此外，BD增强了胃癌细胞对阿霉素的化学敏感性。本研究表明BD可能用作治疗胃癌患者的候选药物。
