Department of Gastroenterology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China.
Molecular Oncology Laboratory, Department of Orthopaedic Surgery and Rehabilitation Medicine, The University of Chicago Medical Center, Chicago, IL, USA.
Ann Med. 2023 Dec;55(1):954-964. doi: 10.1080/07853890.2023.2166980.
BACKGROUND/AIMS: Colorectal cancer is the third leading cause of death in patients with cancers in America. Monensin has represented anti-cancer effect on various human cancer cells. We seek to investigate the effect of monensin on proliferation of human colorectal cancer cells and explore whether IGF1R signaling pathway is involved in anti-cancer mechanism of monensin.
Cell proliferation and migration were assessed by crystal violet staining and cell wounding assay respectively. Cell apoptosis was analyzed by Hoechst 33258 staining and flow cytometry. Cell cycle progression was detected with the use of flow cytometry. Cancer-associated pathways were assessed with the use of pathway-specific reporters. Gene expression was detected by touchdown-quantitative real-time PCR. Inhibition of IGF1R was tested by immunofluorescence staining. Inhibition of IGF1R signaling was accomplished by adenovirus-mediated expression of IGF1.
We found that monensin not only effectively inhibited cell proliferation, cell migration as well as cell cycle progression, but also induced apoptosis and G1 arrest in human colorectal cancer cells. Monensin was shown to target multiple cancer-related signaling pathways such as Elk1, AP1, as well as Myc/max, and suppressed IGF1R expression increasing IGF1 in colorectal cancer cells.
Monensin could suppressed IGF1R expression increasing IGF1 in colorectal cancer cells. It has the potential to be repurposed as an anti-colorectal cancer agent, but further studies are still required to investigate the detailed mechanisms of monensin underlying its anti-cancer motion.Key MessagesMonensin inhibits the cell proliferation and the migration, induces apoptosis and inhibits cell cycle progression in human colorectal cancer cells.Monensin may exert anti-cancer activity by targeting multiple signaling pathways, including the IGF1R signaling pathway.Monensin has the potential to be repurposed as an anti-colorectal cancer agent.
背景/目的：在美国，结直肠癌是癌症患者死亡的第三大主要原因。莫能菌素对各种人类癌细胞表现出抗癌作用。我们旨在研究莫能菌素对人结直肠癌细胞增殖的影响，并探讨 IGF1R 信号通路是否参与莫能菌素的抗癌机制。
通过结晶紫染色和细胞划痕实验分别评估细胞增殖和迁移。通过 Hoechst 33258 染色和流式细胞术分析细胞凋亡。通过流式细胞术检测细胞周期进程。使用通路特异性报告器评估癌症相关途径。通过降落定量实时 PCR 检测基因表达。通过免疫荧光染色检测 IGF1R 的抑制作用。通过腺病毒介导的 IGF1 表达抑制 IGF1R 信号。
我们发现莫能菌素不仅有效抑制细胞增殖、细胞迁移和细胞周期进程，还诱导人结直肠癌细胞凋亡和 G1 期阻滞。莫能菌素靶向多种癌症相关信号通路，如 Elk1、AP1 和 Myc/max，并抑制 IGF1R 表达，增加结直肠癌细胞中的 IGF1。
莫能菌素可抑制 IGF1R 表达，增加结直肠癌细胞中的 IGF1。它有可能被重新用作抗结直肠癌药物，但仍需要进一步研究以探讨莫能菌素抑制其抗癌运动的详细机制。
莫能菌素抑制人结直肠癌细胞的增殖和迁移，诱导凋亡并抑制细胞周期进程。
莫能菌素可能通过靶向包括 IGF1R 信号通路在内的多种信号通路发挥抗癌活性。
莫能菌素有可能被重新用作抗结直肠癌药物。
