姜黄素类似物（2E,6E）-2,6-双（2,3-二甲氧基亚苄基）环己酮（DMCH）对SW620结肠癌细胞系的抗转移作用及其作用机制

Anti-metastasis Effects and Mechanism of Action of Curcumin Analog (2E,6E)-2,6-bis(2,3-dimethoxybenzylidene) Cyclohexanone (DMCH) on the SW620 Colorectal Cancer Cell Line.

作者信息

Rahim Nurul Fattin Che, Hussin Yazmin, Aziz Muhammad Nazirul Mubin, Masarudin Mas Jaffri, Gani Shafinaz Abd, Akhtar Muhammad Nadeem, Abd Rahman Nik Mohd Afizan Nik, Alitheen Noorjahan Banu

机构信息

Department of Cell and Molecular Biology, Faculty of Biotechnology and Biomolecular Sciences, Universiti Putra Malaysia, UPM, Serdang, 43400, Selangor, Malaysia.

Faculty of Dentistry, AIMST University, Bedong, 08100, Kedah, Malaysia.

出版信息

Anticancer Agents Med Chem. 2025;25(11):774-784. doi: 10.2174/0118715206336788241029050155.

DOI:10.2174/0118715206336788241029050155

PMID:39779570

Abstract

BACKGROUND

Colorectal cancer (CRC) is the second-leading cause of cancer-related deaths. Curcumin has been reported to have suppressive effects in CRC and to address the physiological limitations of curcumin, a chemically synthesized curcuminoid analog, known as (2E,6E)-2,6-Bis (2,3-Dimethoxy benzylidine) cyclohexanone (DMCH), was developed and the anti-metastatic and anti-angiogenic properties of DMCH in colorectal cell line, SW620 were examined.

METHODS

The anti-metastatic effects of DMCH were examined in the SW620 cell line by scratch assay, migration, and invasion assay, while for anti-angiogenesis properties of the cells, the mouse aortic ring assay and Human Umbilical Vein Endothelial Cells (HUVEC) assay were conducted. The mechanism of action was determined by microarray-based gene expression and protein analyses.

RESULTS

The wound healing assay demonstrated that wound closure was decreased from 63.63 ± 1.44% at IC treatment to 4.54 ± 0.62% at IC treatment. Significant (p < 0.05) reductions in the percentage of migrated and invaded cells were also observed in SW620, with values of 36.39 ± 3.86% and 44.81 ± 3.54%, respectively. Mouse aortic ring assays demonstrated a significant reduction in the formation of tubes and microvessels. Microarray and protein profiler results revealed that DMCH treatment has modulated several metastases, angiogenesisrelated transcripts, and proteins like Epidermal Growth Factor Receptor (EGFR), TIMP-1 (TIMP Metallopeptidase Inhibitor 1) and Vascular Endothelial Growth Factor (VEGF).

CONCLUSION

DMCH could be a potential anti-cancer agent due to its capability to impede metastasis and angiogenesis activities of the SW620 colorectal cancer cell line in vitro via regulating genes and protein in metastases and angiogenesis-related signalling pathways.

摘要

背景

结直肠癌（CRC）是癌症相关死亡的第二大原因。据报道，姜黄素对结直肠癌有抑制作用，为了解决姜黄素的生理局限性，人们开发了一种化学合成的姜黄素类似物，即（2E，6E）-2，6-双（2，3-二甲氧基亚苄基）环己酮（DMCH），并研究了DMCH在结直肠癌细胞系SW620中的抗转移和抗血管生成特性。

方法

通过划痕试验、迁移和侵袭试验检测DMCH对SW620细胞系的抗转移作用，同时通过小鼠主动脉环试验和人脐静脉内皮细胞（HUVEC）试验检测细胞的抗血管生成特性。通过基于微阵列的基因表达和蛋白质分析确定作用机制。

结果

伤口愈合试验表明，在IC处理时伤口闭合率从63.63±1.44%降至IC处理时的4.54±0.62%。在SW620中也观察到迁移和侵袭细胞百分比显著降低（p<0.05），分别为36.39±3.86%和44.81±3.54%。小鼠主动脉环试验表明，血管和微血管的形成显著减少。微阵列和蛋白质分析结果显示，DMCH处理调节了几种与转移、血管生成相关的转录本和蛋白质，如表皮生长因子受体（EGFR）、TIMP-1（TIMP金属肽酶抑制剂1）和血管内皮生长因子（VEGF）。