Department of Oncology, Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, China.
Jiangsu Province Hospital of Chinese Medicine, Nanjing, China.
Curr Cancer Drug Targets. 2024;24(10):1071-1079. doi: 10.2174/0115680096274757231219072003.
BACKGROUND: Colorectal cancer (CRC) places a heavy burden on global health. Tectorigenin (Tec) is a type of flavonoid-based compound obtained from the Chinese medical herb Leopard Lily Rhizome. It was found to exhibit remarkable anti-tumor properties in previous studies. However, the effect and molecular mechanisms of Tec in colorectal cancer have not been reported. OBJECTIVE: The objective of this study was to explore the action of Tec in proliferation and glycolysis in CRC and the potential mechanism with regard to the long non-coding RNA (lncRNA) CCAT2/micro RNA-145(miR-145) pathway and . METHODS: The anti-tumor effect of Tec in CRC was examined in cell and animal studies, applying Cell Counting Kit-8 (CCK-8) assay as well as xenograft model experiments. Assay kits were utilized to detect glucose consumption and lactate production in the supernatant of cells and animal serum. The expression of the glycolysis-related proteins was assessed by Western Blotting, and levels of lncRNA CCAT2 and miR-145 in CRC tissue specimens and cells were assessed by realtime quantitative PCR (RT-qPCR). RESULTS: Tec significantly suppressed cell glycolysis and proliferative rate in CRC cells. It could decrease lncRNA CCAT2 in CRC cells but increase the expression of miR-145. LncRNA CCAT2 overexpression or inhibition of miR-145 could abolish the inhibitive effects of Tec on the proliferation and glycolysis of CRC cells. The miR-145 mimic rescued the increased cell viability and glycolysis levels caused by lncRNA CCAT2 overexpression. Tec significantly inhibited the growth and glycolysis of CRC xenograft tumor. The expression of lncRNA CCAT2 decreased while the expression of miR-145 increased after Tec treatment . CONCLUSION: Tec can inhibit the proliferation and glycolysis of CRC cells through the lncRNA CCAT2/miR-145 axis. Altogether, the potential targets discovered in this research are of great significance for CRC treatment and new drug development.
背景:结直肠癌(CRC)给全球健康带来了沉重负担。Tectorigenin(Tec)是一种从中国药用植物虎眼万年青根茎中提取的类黄酮化合物。先前的研究发现,它具有显著的抗肿瘤特性。然而,Tec 在结直肠癌中的作用及其分子机制尚未报道。
目的:本研究旨在探讨 Tec 在 CRC 细胞增殖和糖酵解中的作用及其潜在机制,涉及长链非编码 RNA(lncRNA)CCAT2/微小 RNA-145(miR-145)通路。
方法:在细胞和动物研究中,采用细胞计数试剂盒-8(CCK-8)测定法和异种移植模型实验,检测 Tec 在 CRC 中的抗肿瘤作用。应用试剂盒检测细胞上清液和动物血清中的葡萄糖消耗和乳酸生成。通过 Western Blotting 检测糖酵解相关蛋白的表达,实时定量 PCR(RT-qPCR)检测 CRC 组织标本和细胞中 lncRNA CCAT2 和 miR-145 的水平。
结果: Tec 显著抑制 CRC 细胞的糖酵解和增殖率。它可以降低 CRC 细胞中的 lncRNA CCAT2,但增加 miR-145 的表达。lncRNA CCAT2 过表达或抑制 miR-145 可消除 Tec 对 CRC 细胞增殖和糖酵解的抑制作用。miR-145 模拟物可挽救 lncRNA CCAT2 过表达引起的细胞活力和糖酵解水平的增加。 Tec 显著抑制 CRC 异种移植肿瘤的生长和糖酵解。 Tec 治疗后,lncRNA CCAT2 的表达降低,而 miR-145 的表达增加。
结论: Tec 可通过 lncRNA CCAT2/miR-145 轴抑制 CRC 细胞的增殖和糖酵解。总之,本研究发现的潜在靶点对 CRC 的治疗和新药开发具有重要意义。
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