Article Abstract

A novel Camptothecin analogue inhibits colon cancer development and downregulates the expression of miR-155 in vivo and in vitro

Authors: Qian Lin, Leina Ma, Dong Wang, Zhihong Yang, Jin Wang, Zhantao Liu, Guohui Jiang

Abstract

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<0.05) by FL118 both in vivo and in vitro.
Conclusions: FL118 effectively inhibits colon cancer development and downregulates the expression of miR-155 both in vivo and in vitro. With the understanding that miR-155 is closely associated with the pathogenesis and development of colon cancer, its downregulation resulting from FL118 may indicate that miR-155 is likely to participate in, and even mediate the anticancer activity of FL118 on colon carcinoma, which should be noted, and urges further study.

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