A novel Camptothecin analogue inhibits colon cancer development and downregulates the expression of miR-155 in vivo and in vitro
A novel Camptothecin analogue inhibits colon cancer development and downregulates the expression of miR-155 in vivo and in vitro
复制标题
一种新型喜树碱类似物在体内和体外抑制结肠癌的发展并下调 miR-155 的表达
DOI：
10.21037/tcr.2017.06.20
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发表时间：
2017-06-01
影响因子：
0.9
通讯作者：
Jiang, Guohui
中科院分区：
文献类型：
--
作者：
Lin, Qian;Ma, Leina;Jiang, Guohui
背景资料：FL 118是一种新发现的喜树碱类似物，对多种癌症具有抗肿瘤活性;然而，FL 118抗肿瘤活性的分子机制仍远未完全了解。MicroRNA（miRNAs）被认为在人类恶性肿瘤的进展中起重要作用，并且越来越多的证据表明这些小RNA还介导许多天然和/或合成化合物的肿瘤抑制活性。方法：采用MTT法、划痕法、BrdU法和流式细胞仪分别检测FL 118对HCT-116细胞活力、迁移率、增殖、凋亡和细胞周期的影响。建立异种移植瘤模型，观察FL 118对体内肿瘤生长的影响。结果：FL 118可诱导结肠癌细胞凋亡，抑制细胞活力和运动能力，抑制细胞增殖，抑制结肠癌细胞的生长。miR-155水平显著下调（P
Background: FL118 is a newly discovered camptothecin analogue that exerts anti-tumor activity on a wide range of cancers; however, the molecular mechanism underlying FL118's antitumor activity is still far from being completely understood. MicroRNAs (miRNAs) are believed to play an important role in the progression of human malignancies, and increasing evidence shows that these small RNAs also mediates the tumor-suppressing activity of many natural and/or synthetic compounds. Our previous studies indicated that miR-155, which has been confirmed as an oncogenic miRNA in colorectal carcinoma was significantly downregulated after the treatment of FL118.Methods: MTT assay, scratch wound assay, BrdU cell proliferation assay and flow cytometry were employed to detect HCT-116 cell viability, mobility, proliferation, apoptosis and cell cycle under the treatment of FL118, respectively. Xenograft models were established to observe the effect of FL118 on tumor growth in vivo. Also, qRT-PCR was performed to detect the level of miR-155 in colon cancer cells and tumor samples after FL118 administration.Results: Our results showed that FL118 induced cell apoptosis, inhibited cell viability and mobility, suppressed cell proliferation and limited the growth of colon cancer. The levels of miR-155 were downregulated significantly (P