Antitumor effects of matrine on cancer stem like cells isolated from the human liver cancer SMMC-7721 cell line.

The existence of cancer stem cells (CSCs) or cancer stem-like cells (CSLCs) is regarded as the cause of tumor formation and recurrence. Matrine has been reported to exhibit antitumor effects in cancer cells. In the present study, a preliminary study was performed on the mechanisms of matrine on hepatocellular carcinoma (HCC) stem-like cells. The HCC SMMC-7721 cell line was cultured in tumor stem cell-specific medium to form spheres, and different concentrations (1, 2 and 5 mg/kg) of cisplatin were then used in order to purify the most drug-resistant cells, which were used as CSLCs. An MTT assay was performed to detect the inhibitory effects of matrine against CSLC proliferation. Quantitative polymerase chain reaction (qPCR) and western blot analysis were used to detect changes in cell adhesion regulating gene (CAR), E-cadherin, laminin and fibronectin. As a result, using tryptose sulfite cycloserine medium culture and cisplatin-resistance screening, CSLCs were successfully isolated from the SMMC-7721 cell line. Matrine inhibited the proliferation of CSLCs in vitro. The results of qPCR and western blot analysis demonstrated that matrine upregulated the expression of CAR, E-cadherin, laminin and fibronectin in CSLCs compared with the control treatment. A certain concentration of matrine exhibited antitumor effects on HCC stem like cells.

[1]  H. Cai,et al.  Matrine suppresses invasion and metastasis of NCI-H1299 cells by enhancing microRNA-133a expression. , 2015, International journal of clinical and experimental medicine.

[2]  Irving L Weissman,et al.  Cancer stem cells--perspectives on current status and future directions: AACR Workshop on cancer stem cells. , 2006, Cancer research.

[3]  Effect of Matrine on HPAC cell migration by down-regulating the expression of MT1-MMP via Wnt signaling , 2015, Cancer Cell International.

[4]  A. Ross,et al.  Cancer stem cells: Cell culture, markers, and targets for new therapies , 2009, Journal of cellular biochemistry.

[5]  M. Araie,et al.  Sphere formation and expression of neural proteins by human corneal stromal cells in vitro. , 2005, Investigative ophthalmology & visual science.

[6]  Ming Niu,et al.  Anti-hepatitis B virus effect of matrine-type alkaloid and involvement of p38 mitogen-activated protein kinase and tumor necrosis factor receptor-associated factor 6. , 2016, Virus research.

[7]  J. Chang,et al.  Current Status and Issues in Cancer Stem Cell Study , 2008, Cancer investigation.

[8]  Guo-yu Li,et al.  Hepatoprotective effect of Matrine salvianolic acid B salt on Carbon Tetrachloride-Induced Hepatic Fibrosis , 2012, Journal of Inflammation.

[9]  Jing Wang,et al.  Matrine induces mitochondrial apoptosis in cisplatin-resistant non-small cell lung cancer cells via suppression of β-catenin/survivin signaling. , 2015, Oncology reports.

[10]  H. Wang,et al.  A subpopulation of CD24⁺ cells in colon cancer cell lines possess stem cell characteristics. , 2012, Neoplasma.

[11]  Xiaoya Li,et al.  Anti-tumor activities of matrine and oxymatrine: literature review , 2014, Tumor Biology.

[12]  Zang Ai-hua,et al.  Stem Cells,Cancer and Cancer Stem Cells , 2005 .

[13]  M. Shen,et al.  A luminal epithelial stem cell that is a cell of origin for prostate cancer , 2009, Nature.

[14]  Y. Atomi,et al.  Coexpression of Matrilysin and Laminin-5 γ2 Chain May Contribute to Tumor Cell Migration in Colorectal Carcinomas , 2003, Digestive Diseases and Sciences.

[15]  Q. Kan,et al.  Protective effects of matrine on experimental autoimmune encephalomyelitis via regulation of ProNGF and NGF signaling. , 2016, Experimental and molecular pathology.

[16]  Y. Miao,et al.  Epithelial mesenchymal transition correlates with CD24+CD44+ and CD133+ cells in pancreatic cancer. , 2012, Oncology reports.

[17]  M. Todaro,et al.  Single-cell cloning of colon cancer stem cells reveals a multi-lineage differentiation capacity , 2008, Proceedings of the National Academy of Sciences.

[18]  F. Mohammadizadeh,et al.  Correlation of E-cadherin expression and routine immunohistochemistry panel in breast invasive ductal carcinoma. , 2009, Cancer biomarkers : section A of Disease markers.

[19]  M. Rubin,et al.  E-cadherin expression in primary carcinomas of the breast and its distant metastases , 2003, Breast Cancer Research.

[20]  Yan Liu,et al.  Matrine derivative WM130 inhibits hepatocellular carcinoma by suppressing EGFR/ERK/MMP-2 and PTEN/AKT signaling pathways. , 2015, Cancer letters.

[21]  Hiroyuki Yamamoto,et al.  Association of reduced cell adhesion regulator messenger RNA expression with tumor progression in human hepatocellular carcinoma , 1997, International journal of cancer.

[22]  M. Caligiuri,et al.  A cell initiating human acute myeloid leukaemia after transplantation into SCID mice , 1994, Nature.

[23]  H. Asakura,et al.  Gross appearance of hepatocellular carcinoma reflects E‐cadherin expression and risk of early recurrence after surgical treatment , 2003, Journal of gastroenterology and hepatology.

[24]  Matrine suppresses proliferation and induces apoptosis in human cholangiocarcinoma cells through suppression of JAK2/STAT3 signaling. , 2015, Pharmacological reports : PR.

[25]  S. Morrison,et al.  Prospective identification of tumorigenic breast cancer cells , 2003, Proceedings of the National Academy of Sciences of the United States of America.

[26]  J. Zhang,et al.  Antifibrotic effects of matrine on in vitro and in vivo models of liver fibrosis in rats. , 2001, Acta pharmacologica Sinica.

[27]  H. Frierson,et al.  The metastasis-associated gene CD24 is regulated by Ral GTPase and is a mediator of cell proliferation and survival in human cancer. , 2006, Cancer research.

[28]  P. Dirks,et al.  Cancer stem cells in nervous system tumors , 2004, Oncogene.

[29]  C. Jordan.  Cancer stem cell biology: from leukemia to solid tumors. , 2004, Current opinion in cell biology.