Epigenetic silence of lumican inhibits the motility of colon cancer via inactivating MAPK signaling in vitro and in vivo

被引：0
作者：
Quan, Fengtao [1 ]
Chen, Yongle [2 ]
Hao, Dongming [3 ]
Zhang, Li [3 ]
Yang, Weizhen [1 ]
机构：
[1] Baoji Ctr Hosp, Dept Gen Surg, 8 Jiang Tan Rd, Baoji, Shaanxi, Peoples R China
[2] Baoji Ctr Hosp, Dept Anus & Intestine Surg, Baoji, Peoples R China
[3] Tianjin Peoples Hosp, Dept Anus & Intestine Surg, Tianjin, Peoples R China
来源：
INTERNATIONAL JOURNAL OF CLINICAL AND EXPERIMENTAL MEDICINE | 2017年 / 10卷 / 06期
关键词：
Lumican; colon cancer; invasion; migration; ERK; EXTRACELLULAR-MATRIX; METASTASIS; CELLS; EXPRESSION; GROWTH; COMPONENTS; INVASION; PROTEIN;
D O I：
暂无
中图分类号：
R-3 [医学研究方法]; R3 [基础医学];
学科分类号：
1001 ;
摘要：
Objective: To explore the effects of lumican on invasion and migration abilities of colon cancer cells and the relevant mechanism. Methods: The expression of lumican in four colon cancer cell lines (SW480, SW620, HCT-8 and LOVO) and the human colonic epithelial cells CCD-18Co was detected by western blotting. Lumican was silenced by constructing lentivirus and transfecting into SW480 and HCT-8 cells. The efficiency of silencing was detected by qRT-PCR and western blotting. The effect of lumican siRNA on invasion and migration of colon cancer cells was detected by transwell assay and wound scratch assay. The expression of metastasis-related proteins vascular endothelial growth factor (VEGF) and metal matrix proteinase (MMP)-9 was detected by western blotting. The level of ERK1, p-ERK1, JNK and p-JNK was also detected by western blotting. Finally, the effects of lumican on tumor growth and metastasis were detected in colon cancer xenograft. Results: The expression level of lumican was significantly increased in colon cell lines compared with CCD-18Co. Lumican was then silenced by transfecting siRNA into SW480 and HCT-8 cells. The decreased invasive cell number with reduced wound closing rate was detected in SW480 and HCT-8 cells transfected with lumican siRNA compared with control group. The decreased level of metastasis-related proteins VEGF and MMP-9 further convinced the inhibitory effect of lumican siRNA transfection on the motility of colon cancer. In addition, the expression of ERK/JNK pathway proteins was strongly suppressed under lumican siRNA treatment. Finally, the in vivo experiment revealed that lumican-siRNA strongly reduced the tumor growth and tumor volume. Besides, lumican-siRNA transfection inhibited tumor metastasis via suppressing the expression of metastasis-related proteins. The level of p-ERK1/2 and p-JNK was also reduced treated with lumican-siRNA. Conclusions: The inhibiting of lumican restrains the invasion and migration abilities of colon cancer and may through inhibiting ERK/JNK signaling pathway. Lumican may become a biological marker for predicting progression and prognosis of colon cancer.
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页码：8875 / 8883
页数：9
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