Scutellaria barbata D. Don inhibits colorectal cancer growth via suppression of Wnt/β-catenin signaling pathway

Li-hui Wei; Jiu-mao Lin; Jian-feng Chu; Hong-wei Chen; Qing-yu Li; Jun Peng

doi:10.1007/s11655-017-2775-3

Your Location：

Home >

Browse articles >

Scutellaria barbata D. Don inhibits colorectal cancer growth via suppression of Wnt/β-catenin signaling pathway

Updated：2021-08-27

- Scutellaria barbata D. Don inhibits colorectal cancer growth via suppression of Wnt/β-catenin signaling pathway
- Chinese Journal of Integrative Medicine Vol. 23, Issue 11, Pages: 858-863(2017)
- Affiliations：
  
  1. Academy of Integrative Medicine, Fujian University of Traditional Chinese Medicine,Fuzhou,China
  2. Fujian Key Laboratory of Integrative Medicine on Geriatrics, Fujian University of Traditional Chinese Medicine,Fuzhou,China
- Author bio：
- Funds：
  
  Supported by the Natural Science Foundation of Fujian Province of China (No. 2013J01333), the Youth Science Foundation of the Health Department of Fujian Province (2012-2-60) and the Developmental Fund of Chen Keji Integrative Medicine (No. CKJ2015008)
- DOI：10.1007/s11655-017-2775-3
  CLC：
- Published：2017，
  
  Published Online：28 October 2017，
Scan for full text
Wei, Lh., Lin, Jm., Chu, Jf. et al. Scutellaria barbata D. Don inhibits colorectal cancer growth via suppression of Wnt/β-catenin signaling pathway., Chin. J. Integr. Med. 23, 858–863 (2017). https://doi.org/10.1007/s11655-017-2775-3

Li-hui Wei, Jiu-mao Lin, Jian-feng Chu, et al. Scutellaria barbata D. Don inhibits colorectal cancer growth via suppression of Wnt/β-catenin signaling pathway. [J]. Chinese Journal of Integrative Medicine 23(11):858-863(2017)
Wei, Lh., Lin, Jm., Chu, Jf. et al. Scutellaria barbata D. Don inhibits colorectal cancer growth via suppression of Wnt/β-catenin signaling pathway., Chin. J. Integr. Med. 23, 858–863 (2017). https://doi.org/10.1007/s11655-017-2775-3 DOI：

Li-hui Wei, Jiu-mao Lin, Jian-feng Chu, et al. Scutellaria barbata D. Don inhibits colorectal cancer growth via suppression of Wnt/β-catenin signaling pathway. [J]. Chinese Journal of Integrative Medicine 23(11):858-863(2017) DOI： 10.1007/s11655-017-2775-3.

摘要

To investigate the effect of the ethanol extract of Scutellaria barbata D. Don (EESB) on colorectal cancer (CRC) growth and Wnt/β-catenin signaling pathway in vivo and in vitro. In vivo experiment

CRC xenograft mouse model was constructed with injection of HT-29 cells. Following xenograft implantation

twenty mice were randomly divided into EESB-treated group (n=10) and control group (n=10) by a random number table

and were given with intra-gastric administration of 2 g/kg EESB or saline

5 days a week for 16 days

respectively. At the end of experiment

tumors were removed and weighed by electronic scales. The proliferation biomarker Ki-67 of tumor was evaluated by immunohistochemistry (IHC) assay. In vitro study

HT-29 cells were treated with 0

0.5

1.5

2.5 mg/mL EESB for 24 h. At the end of the treatment

the viability and survival of HT-29 cells were determined by methylthiazolyldiphenyl-tetrazolium bromide (MTT) assay and colony formation assay

respectively. The mRNA expression of c-Myc

Survivin and adenomatous polyposis coli (APC) was examined by reverse transcription-polymerase chain reaction (RT-PCR) both in tumor tissues of CRC xenograft mice and HT-29 cells. Protein expression of c-Myc

Survivin

APC

and β-catenin as well as β-catenin phosphorylation level were evaluated by IHC assay or Western blotting. EESB significantly reduced tumor weight in CRC xenografts mice

compared with the control group (P<0.05). IHC assay showed that EESB significantly inhibited protein expression of Ki-67 in tumor tissues (P<0.05). MTT assay showed that EESB significantly reduced HT-29 cell viability in a dose-dependent manner (P<0.05). Colony formation assay showed that EESB dose-dependently decreased the survival of HT-29 cells (P<0.05). In addition

RT-PCR assay showed that EESB decreased the mRNA expression of c-Myc and Survivin and increased APC expression

both in tumor tissues of CRC xenograft mice and HT-29 cells (P<0.05). IHC assay or Western blotting showed that EESB decreased protein expression of β-catenin

c-Myc and Survivin

as well as increased APC expression and β-catenin phosphorylation in tumor tissues or HT-29 cells (P<0.05). EESB significantly reduced tumor growth in CRC xenografts mice

and inhibited the viability and survival of HT-29 cells. EESB could suppress the activation of the Wnt/β-catenin pathway

which might be one of the mechanisms whereby Scutellaria barbata D. Don exerts its anticancer activity.

Abstract

To investigate the effect of the ethanol extract of Scutellaria barbata D. Don (EESB) on colorectal cancer (CRC) growth and Wnt/β-catenin signaling pathway in vivo and in vitro. In vivo experiment

CRC xenograft mouse model was constructed with injection of HT-29 cells. Following xenograft implantation

twenty mice were randomly divided into EESB-treated group (n=10) and control group (n=10) by a random number table

and were given with intra-gastric administration of 2 g/kg EESB or saline

5 days a week for 16 days

respectively. At the end of experiment

tumors were removed and weighed by electronic scales. The proliferation biomarker Ki-67 of tumor was evaluated by immunohistochemistry (IHC) assay. In vitro study

HT-29 cells were treated with 0

0.5

1.5

2.5 mg/mL EESB for 24 h. At the end of the treatment

the viability and survival of HT-29 cells were determined by methylthiazolyldiphenyl-tetrazolium bromide (MTT) assay and colony formation assay

respectively. The mRNA expression of c-Myc

Survivin

APC

and β-catenin as well as β-catenin phosphorylation level were evaluated by IHC assay or Western blotting. EESB significantly reduced tumor weight in CRC xenografts mice

RT-PCR assay showed that EESB decreased the mRNA expression of c-Myc and Survivin and increased APC expression

both in tumor tissues of CRC xenograft mice and HT-29 cells (P<0.05). IHC assay or Western blotting showed that EESB decreased protein expression of β-catenin

c-Myc and Survivin

as well as increased APC expression and β-catenin phosphorylation in tumor tissues or HT-29 cells (P<0.05). EESB significantly reduced tumor growth in CRC xenografts mice

and inhibited the viability and survival of HT-29 cells. EESB could suppress the activation of the Wnt/β-catenin pathway

which might be one of the mechanisms whereby Scutellaria barbata D. Don exerts its anticancer activity.

关键词

Scutellaria barbata D. Doncolorectal cancerproliferationWnt/β-catenin pathway

Keywords

Scutellaria barbata D. Doncolorectal cancerproliferationWnt/β-catenin pathway

references

Siegel R, Desantis C, Jemal A. Colorectal cancer statistics, 2014. CA Cancer J Clin 2014;64:104–117.

Evan GI, Vousden KH. Proliferation, cell cycle and apoptosis in cancer. Nature 2001;411:342–348.

Klaus A, Birchmeier W. Wnt signalling and its impact on development and cancer. Nat Rev Cancer 2008;8:387–398.

Moravec M. Colorectal cancer and canonical Wnt signalling pathway. Cas Lek Cesk 2012;151:335–342.

Gupta A, Verma A, Mishra AK, Wadhwa G, Sharma SK, Jain CK. The Wnt pathway: emerging anticancer strategies. Recent Pat Endocr Metab Immune Drug Discov 2013;7:138–147.

Dihlmann S, von Knebel Doeberitz M. Wnt/beta-cateninpathway as a molecular target for future anti-cancer therapeutics. Int J Cancer 2005;113:515–524.

Minde DP, Anvarian Z, Rüdiger SG, Maurice MM. Messing up disorder: how do missense mutations in the tumor suppressor protein APC lead to cancer? Mol Cancer 2011;10:101.

Rao TP, Kühl M. An updated overview on Wnt signaling pathways: A prelude for more. Circ Res 2010;106:1798–1806.

MacDonald BT, Tamai K, He X. Wnt/ß-catenin signaling: components, mechanisms, and diseases. Dev Cell 2009;17:9–26.

Logan CY, Nusse R. The Wnt signaling pathway in development and disease. Annu Rev Cell Dev Biol 2004;20:781–810.

Hernández-Maqueda JG, Luna-Ulloa LB, Santoyo-Ramos P, Castañeda-Patlán MC, Robles-Flores M. Protein kinase C delta negatively modulates canonical Wnt pathway and cell proliferation in colon tumor cell lines. PLoS One 2013;8:e58540.

Gehrke I, Gandhirajan RK, Kreuzer KA. Targeting the WNT/ beta-catenin/TCF/LEF1 axis in solid and haematological cancers: Multiplicity of therapeutic options. Eur J Cancer 2009;45:2759–2767.

Yin X, Zhou J, Jie C, Xing D, Zhang Y. Anticancer activity and mechanism of Scutellaria barbata extract on human lung cancer cell line A549. Life Sci 2004;75:2233–2244.

Chinese Pharmacopoeia Commission. Pharmacopoeia of the Peoples Republic of China. Beijing: China Medical Scientific Techology Press; 2010:109–110.

Tan P, Lu BZ, Bao WL. Analysis on the clinical application of Scutellaria barbata D. Don in the anti-cancer therapy. J Jiangxi Tradit Chin Med (Chin) 2006;37:57–58.

Liu T, Wang XY, Zeng ZQ. The pharmacological effects and clinical application research progress of Scutellaria barbata D. Don. J Henan Tradit Chin Med (Chin) 2013;3:424–426.

Wei L, Lin J, Wu G, Xu W, Li H, Hong Z, et al. Scutellaria barbata D. Don induces G1/S arrest via modulation of p53 and Akt pathways in human colon carcinoma cells. Oncol Rep 2013;29:1623–1628.

Wei L, Chen Y, Lin J, Zhao J, Chen X, Xu W, et al. Scutellaria barbata D. Don induces apoptosis of human colon carcinoma cell through activation of the mitochondriondependent pathway. J Med Plants Res 2011;5:1962–1970.

Wei L, Lin J, Xu W, Hong Z, Liu X, Peng J. Inhibition of tumor angiogenesis by Scutellaria barbata D. Don via suppressing proliferation, migration and tube formation of endothelial cells and downregulation of the expression of VEGF-A in cancer cells. J Med Plants Res 2011;5:3260–3268.

Wei L, Lin J, Xu W, Cai Q, Shen A, Hong Z, et al. Scutellaria barbata D. Don inhibits tumor angiogenesis via suppression of hedgehog pathway in a mouse model of colorectal cancer. Int J Mol Sci 2012;13:9419–9430.

Lin J, Chen Y, Cai Q, Wei L, Zhan Y, Shen A, et al. Scutellaria barbata D Don inhibits colorectal cancer growth via suppression of multiple signaling pathways. Integr Cancer Ther 2013;13:240–248.

Yamulla RJ, Kane EG, Moody AE, Politi KA, Lock NE, Foley AV, et al. Testing models of the APC tumor suppreßsor/ ß-catenin interaction reshapes our view of the destruction complex in Wnt signaling. Genetics 2014;197:1285–1302.

Bertrand FE, Angus CW, Partis WJ, Sigounas G. Developmental pathways in colon cancer: crosstalk between WNT, BMP, Hedgehog and Notch. Cell Cycle 2012;11:4344–4351.

Yokota T. Are KRAS/BRAF mutations potent prognostic and/or predictive biomarkers in colorectal cancers? Anticancer Agents Med Chem 2012;12:163–171.

Waldner MJ, Foersch S, Neurath MF. Interleukin-6-a key regulator of colorectal cancer development. Int J Biol Sci 2012;8:1248–1253.

Dimova I, Popivanov G, Djonov V. Angiogenesis in cancergeneral pathways and their therapeutic implications. J BUON 2014;19:15–21.

Li ST, Chi P. Evolution of the management of colorectal cancer using integrative medicine. Chin J Integr Med 2011;17:73–79.

Demir L, Ekinci N, Erten C, Somali I, Can A, Dirican A, et al. The impact of cell proliferation markers and p53 mutation status on prognosis of non-metastatic colon cancer. J Surg Oncol 2014;109:665–675.

FULL TEXT LINK

More>

Views

Downloads

CSCD

Alert me when the article has been cited

Submit

Tools

Publicity Resources

Effects of Jianpi Jiedu Recipe (健脾解毒方) on reversion of P-glycoprotein-mediated multidrug resistance through COX-2 pathway in colorectal cancer

Nodule and eminence on frenulum labii superioris: Diagnostic markers for metastatic colorectal cancer

The ethanol extract isolated from Weiqi Decoction (胃祺饮) induces G2/M arrest and apoptosis in AGS cells

Effects of Danshen Injection (丹参注射液) on inhibiting proliferation and inducing apoptosis through down-regulation of mutant JAK2 gene and its protein phosphorylation in human erythroid leukemic cells

Xihuang Pill (西黄丸) induces mesenchymal-epithelial transition and inhibits loss of apical-basal polarity in colorectal cancer cell through regulating ZEB1-SCRIB Loop

Related Author

No data

Related Institution

Department of Chemistry, University of South Florida

Department of Biomedical Sciences, Cornell University, Ithaca

Department of Molecular Oncology, H. Lee Moffitt Cancer Center and Research Institute

Department of Medical Oncology, Shuguang Hospital & Putuo Hospital, Shanghai University of Traditional Chinese Medicine

Tianjin Medical University

Address：1 Caochang, xiyuan, Beijing, People's Republic of China Postal code：100091
Tel：010-62886827, 62877592 Fax：010-62874291
Technical support is provided by Beijing Founder electronics co., LTD 京ICP备05067934号-1 京公网安备11010802024621
It is recommended to read the content of this site in Chrome&IE9+. Please switch to extreme mode in browser 360.
Cookies We use cookies to help provide and enhance our service and tailor content. By continuing, you agree to the use of cookies.

⁰