Natural small molecule bigelovin suppresses orthotopic colorectal tumor growth and inhibits colorectal cancer metastasis via IL6/STAT3 pathway
Li, Mingyue1,2; Yue, Grace Gar-Lee2,3; Song, Li-Hua4; Huang, Mao-Bo5; Lee, Julia Kin-Ming2,3; Tsui, Stephen Kwok-Wing1; Fung, Kwok-Pui1,2,3; Tan, Ning-Hua4,5; Lau, Clara Bik-San2,3
2018-04-01
发表期刊BIOCHEMICAL PHARMACOLOGY
ISSN0006-2952
卷号150页码:189-199
摘要Bigelovin, a sesquiterpene lactone, has been demonstrated to induce apoptosis, inhibit inflammation and angiogenesis in vitro, but its potential anti-metastatic activity remains unclear. In the present study, two colon cancer mouse models, orthotopic tumor allografts and experimental metastatic models were utilized to investigate the progression and metastatic spread of colorectal cancer after bigelovin treatments. Results showed that bigelovin (intravenous injection; 0.3-3 mg/kg) significantly suppressed tumor growth and inhibited liver/ lung metastasis with modulation of tumor microenvironment (e.g. increased populations of T lymphocytes and macrophages) in orthotopic colon tumor allograft-bearing mice. Furthermore, the inhibitory activities were also validated in the experimental human colon cancer metastatic mouse model. The underlying mechanisms involved in the anti-metastatic effects of bigelovin were then revealed in murine colon tumor cells colon 26-M01 and human colon cancer cells HCT116. Results showed that bigelovin induced cytotoxicity, inhibition of cell proliferation, motility and migration in both cell lines, which were through interfering II.6/STAT3 and cofilin pathways. Alternations of the key molecules including Rock, FAK, RhoA, Rac1/2/3 and N-cadherin, which were detected in bigelovin-treated cancer cells, were also observed in the tumor allografts of bigelovin-treated mice. These findings strongly indicated that bigelovin has potential to be developed as anti-tumor and anti-metastatic agent for colorectal cancer.
关键词Bigelovin Colorectal Cancer Metastasis Tumor Microenvironment Ll6/stat3 Pathway
DOI10.1016/j.bcp.2018.02.017
语种英语
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文献类型期刊论文
条目标识符http://ir.kib.ac.cn/handle/151853/61251
专题植物化学与西部植物资源持续利用国家重点实验室
作者单位1.Chinese Univ Hong Kong, Sch Biomed Sci, Shatin, Hong Kong, Peoples R China
2.Chinese Univ Hong Kong, Inst Chinese Med, Shatin, Hong Kong, Peoples R China
3.Chinese Univ Hong Kong, State Key Lab Phytochem & Plant Resources West Ch, Shatin, Hong Kong, Peoples R China
4.China Pharmaceut Univ, Sch Tradit Chinese Pharm, 639 Longmian Ave, Nanjing 211198, Jiangsu, Peoples R China
5.Chinese Acad Sci, Kunming Inst Bot, State Key Lab Phytochem & Plant Resources West Ch, Kunming 650201, Yunnan, Peoples R China
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Li, Mingyue,Yue, Grace Gar-Lee,Song, Li-Hua,et al. Natural small molecule bigelovin suppresses orthotopic colorectal tumor growth and inhibits colorectal cancer metastasis via IL6/STAT3 pathway[J]. BIOCHEMICAL PHARMACOLOGY,2018,150:189-199.
APA Li, Mingyue.,Yue, Grace Gar-Lee.,Song, Li-Hua.,Huang, Mao-Bo.,Lee, Julia Kin-Ming.,...&Lau, Clara Bik-San.(2018).Natural small molecule bigelovin suppresses orthotopic colorectal tumor growth and inhibits colorectal cancer metastasis via IL6/STAT3 pathway.BIOCHEMICAL PHARMACOLOGY,150,189-199.
MLA Li, Mingyue,et al."Natural small molecule bigelovin suppresses orthotopic colorectal tumor growth and inhibits colorectal cancer metastasis via IL6/STAT3 pathway".BIOCHEMICAL PHARMACOLOGY 150(2018):189-199.
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