吴茱萸碱通过诱导细胞凋亡和自噬发挥抗癌作用，并抑制人结肠癌细胞的迁移和侵袭。

Evodiamine exerts anticancer effects via induction of apoptosis and autophagy and suppresses the migration and invasion of human colon cancer cells.

作者信息

Wang Dan, Ge Shuke, Chen Zhe, Song Yongwei

机构信息

Department of General Surgery, the third People's Hospital of Dalian, Dalian Medical University, Dalian, Liaoning Province, China, 116034.

出版信息

J BUON. 2019 Sep-Oct;24(5):1824-1829.

PMID:31786843

Abstract

PURPOSE

Colon cancer ranks as the fourth common type of cancer and is responsible for significant morbidity and mortality throughout the world. Late diagnosis and the rarity of potent and safer chemotherapeutic drugs and efficient therapeutic targets create severe obstacle in the treatment of colon cancer. This study was undertaken to examine the anticancer effects of Evodiamine against human colon cancer cells.

METHODS

The proliferation rate of the SW480 colon cancer cells was monitored by MTT assay. Apoptosis was detected by Annexin V/propidium iodide (PI) and acridine orange (AO)/ethidium bromide (EB) staining. Transmission electron microscopy (TEM) was used for detection of autophagy. Cell migration and invasion was detected by wound healing and transwell assays, respectively. Protein expression was determined by western blotting.

RESULTS

Evodiamine suppressed the proliferation of the SW480 colon cancer cells and exhibited an IC50 of 10 µM. The cytotoxic effects of Evodiamine were found to be comparatively lower against the normal CDD-18Co colon cells as evidenced from the IC50 of 100 µM. AO/EB staining showed that Evodiamine caused apoptosis of the SW480 cells and the percentage of the apoptotic SW480 cells increased with increase in the Evodiamine concentration as indicated by annexin V/PI staining. Evodiamine-induced apoptosis was also accompanied by upregulation of caspase-3 and Bax and suppression of Bcl-2. TEM analysis showed that Evodiamine also activated autophagy in the SW480 cells by enhancing the expression of LC3 II and Beclin 1. The wound assay showed that Evodiamine suppressed the migration of the SW480 cells. Evodiamine also reduced the invasion potential of the SW480 cells as suggested by the transwell assay.

CONCLUSION

The findings of the present study suggest that Evodiamine is a potent anticancer agent and may prove beneficial in the development of systemic therapy of colon cancer.

摘要

目的

结肠癌是全球第四大常见癌症类型，在全球范围内导致了显著的发病率和死亡率。晚期诊断以及高效、安全的化疗药物和有效治疗靶点的稀缺，给结肠癌的治疗带来了严重障碍。本研究旨在探讨吴茱萸碱对人结肠癌细胞的抗癌作用。

方法

采用MTT法监测SW480结肠癌细胞的增殖率。通过Annexin V/碘化丙啶（PI）和吖啶橙（AO）/溴化乙锭（EB）染色检测细胞凋亡。采用透射电子显微镜（TEM）检测自噬。分别通过划痕愈合实验和Transwell实验检测细胞迁移和侵袭能力。通过蛋白质免疫印迹法测定蛋白质表达。

结果

吴茱萸碱抑制SW480结肠癌细胞的增殖，IC50为10 μM。从IC50为100 μM可知，吴茱萸碱对正常CDD-18Co结肠细胞的细胞毒性作用相对较低。AO/EB染色显示吴茱萸碱可导致SW480细胞凋亡，Annexin V/PI染色表明，随着吴茱萸碱浓度的增加，凋亡的SW480细胞百分比增加。吴茱萸碱诱导的细胞凋亡还伴随着caspase-3和Bax的上调以及Bcl-2的抑制。TEM分析表明，吴茱萸碱还通过增强LC3 II和Beclin 1的表达激活SW480细胞中的自噬。划痕实验表明吴茱萸碱抑制SW480细胞的迁移。Transwell实验表明吴茱萸碱还降低了SW480细胞的侵袭能力。