Astrocyte elevated gene-1 (AEG-1) shRNA sensitizes Huaier polysaccharide (HP)-induced anti-metastatic potency via inactivating downstream P13K/Akt pathway as well as augmenting cell-mediated immune response

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• 作者：Jiasheng Zheng (1) (2)
  Cong Li (1) (2)
  Xia Wu (3)
  Mengmeng Liu (4)
  Xicai Sun (5)
  Yingzhuo Yang (3)
  Meijun Hao (1) (2)
  Shoupeng Sheng (1) (2)
  Yu Sun (1) (2)
  Honghai Zhang (1) (2)
  Jiang Long (1) (2)
  Yi Liang (6) (7)
  Caixia Hu (1) (2)
  
• 关键词：Anti ; metastasis ; Astrocyte elevated gene ; 1 (AEG ; 1) ; Hepatocellular carcinoma (HCC) ; MHCC97 ; H cells ; Huaier polysaccharide ; P13K/Akt pathway ; NK cell
• 刊名：Tumor Biology
• 出版年：2014
• 出版时间：May 2014
• 年：2014
• 卷：35
• 期：5
• 页码：4219-4224
• 全文大小：
• 参考文献：1. Fischer PB. Is mda-7/IL-24 a 鈥渕agic bullet鈥?for cancer? Cancer Res. 2005;65:10128鈥?8. CrossRef
  2. Price JT, Thompson EW. Mechanisms of tumour invasion and metastasis: emerging targets for therapy. Expert Opin Ther Targets. 2002;6:217鈥?3. CrossRef
  3. Bengmark S, Hafstr枚m L. The natural history of primary and secondary malignant tumors of the liver. I. The prognosis for patients with hepatic metastases from colonic and rectal carcinoma by laparotomy. Cancer. 1969;23:198鈥?02. CrossRef
  4. Zheng J, Li C, Wu X, Yang Y, Hao M, Sheng S, Sun Y, Zhang H, Long J, Hu C. Astrocyte elevated gene-1 is a novel biomarker of epithelial鈥搈esenchymal transition and progression of hepatocellular carcinoma in two China regions. Tumour Biol. 2013. doi:10.1007/s13277-013-1300-3 .
  5. Zheng J, Li C, Wu X, Liu M, Sun X, Yang Y, Hao M, Sheng S, Sun Y, Zhang H, Long J, Liang Y, Hu C. Huaier polysaccharides suppresses hepatocarcinoma MHCC97-H cell metastasis via inactivation of EMT and AEG-1 pathway. Int J Biol Macromol. 2013. doi:10.1016/j.ijbiomac.2013.11.034 .
  6. Yoo BK, Gredler R, Vozhilla N, Su ZZ, Chen D, Forcier T, et al. Identification of genes conferring resistance to 5-fluorouracil. Proc Natl Acad Sci U S A. 2009;106:12938鈥?3. CrossRef
  7. Kock N, Kasmieh R, Weissleder R, Shah K. Tumor therapy mediated by lentiviral expression of shBcl-2 and S-TRAIL. Neoplasia. 2007;9:435鈥?2. CrossRef
  8. Yang SF, Yang WE, Kuo WH, Chang HR, Chu SC, Hsieh YS. Antimetastatic potentials of flavones on oral cancer cell via an inhibition of matrix-degrading proteases. Arch Oral Biol. 2008;53:287鈥?4. CrossRef
  9. Chu SC, Yang SF, Liu SJ, Kuo WH, Chang YZ, Hsieh YS. In vitro and in vivo antimetastatic effects of / Terminalia catappa L. leaves on lung cancer cells. Food Chem Toxicol. 2007;45:1194鈥?01. CrossRef
  10. Yang SF, Yang WE, Chang HR, Chu SC, Hsieh YS. Luteolin induces apoptosis in oral squamous cancer cells. J Dent Res. 2008;87:401鈥?. CrossRef
  11. Srivastava J, Siddiq A, Emdad L, Santhekadur PK, Chen D, Gredler R, et al. Astrocyte elevated gene-1 promotes hepatocarcinogenesis: novel insights from a mouse model. Hepatology. 2012;56:1782鈥?1. CrossRef
  12. Emdad L, Sarkar D, Lee SG, Su ZZ, Yoo BK, Dash R, et al. Astrocyte elevated gene-1: a novel target for human glioma therapy. Mol Cancer Ther. 2010;9:79鈥?8. CrossRef
  13. Zhou Z, Deng H, Yan W, Huang H, Deng Y, Li Y, et al. Expression of metadherin/AEG-1 gene is positively related to orientation chemotaxis and adhesion of human hepatocellular carcinoma cell lines of different metastatic potentials. J Huazhong Univ Sci Technol Med Sci. 2012;32:353鈥?. CrossRef
  14. Kim D, Kim S, Koh H, Yoon SO, Chung AS, Cho KS, et al. Akt/PKB promotes cancer cell invasion via increased motility and metalloproteinase production. FASEB J. 2001;15:1953鈥?2. CrossRef
  15. Rao JS. Molecular mechanisms of glioma invasiveness: the role of proteases. Nat Rev Cancer. 2003;3:489鈥?01. CrossRef
  16. Westermarck J, K盲h盲ri VM. Regulation of matrix metalloproteinase expression in tumor invasion. FASEB J. 1999;13:781鈥?2.
  17. Won DP, Lee JS, Kwon DS, Lee KE, Shin WC, Hong EK. Immunostimulating activity by polysaccharides isolated from fruiting body of / Inonotus obliquus. Mol Cells. 2011;31:165鈥?3. CrossRef
  18. Smyth MJ, Trapani JA. Lymphocyte-mediated immunosurveillance of epithelial cancers. Trends Immunol. 2001;22:409鈥?1. CrossRef
  19. Pedersen BK. Natural killer cells in relation to disease and treatment. Allergy. 1985;40:547鈥?7. CrossRef
  20. Wu J, Lanier LL. Natural killer cells and cancer. Adv Cancer Res. 2003;90:127鈥?6. CrossRef
  21. Shen W, Wang H, Guo G, Tuo J. Immunomodulatory effects of / Caulerpa racemosa var peltata polysaccharide and its selenizing product on T lymphocytes and NK cells in mice. Sci China C Life Sci. 2008;51:795鈥?01. CrossRef
  
• 作者单位：Jiasheng Zheng (1) (2)
  Cong Li (1) (2)
  Xia Wu (3)
  Mengmeng Liu (4)
  Xicai Sun (5)
  Yingzhuo Yang (3)
  Meijun Hao (1) (2)
  Shoupeng Sheng (1) (2)
  Yu Sun (1) (2)
  Honghai Zhang (1) (2)
  Jiang Long (1) (2)
  Yi Liang (6) (7)
  Caixia Hu (1) (2)
  
  1. Intervention Therapy Center of Liver Diseases, Beijing You An Hospital, Capital Medical University, Beijing, 100069, China
  2. Beijing Institute of Liver Diseases, Beijing You An Hospital, Capital Medical University, Beijing, 100069, China
  3. Department of Infectious Disease, The Second Affiliated Hospital of Harbin Medical University, Harbin, 150081, China
  4. Department of Pharmacology, College of Pharmacy, Harbin Medical University, Harbin, 150081, China
  5. School of Medicine, Tsinghua Center for Life Sciences, Tsinghua University, Beijing, 100084, China
  6. Department of Nutrition and Food Hygiene, Public Health College of Guiyang Medical College, Guiyang, 550000, China
  7. School of Public Health, Shenyang Medical College, Shenyang, 110034, China
  
• ISSN：1423-0380

文摘

Astrocyte elevated gene-1 (AEG-1) is an important force in the development and progression of hepatocellular carcinoma (HCC). To extend our study, we examined here the role of AEG-1 in anti-metastatic effects of Huaier polysaccharide (HP) on the human HCC MHCC97-H cell line. AEG-1 shRNA contributed to the anti-proliferation effect of HP on MHCC97-H cells. Furthermore, results of Transwell insert chambers showed that low expression of AEG-1 could effectively facilitate HP to suppress MHCC97-H cell migration and invasion. We achieved this by reducing phosphoinositide 3-kinases (P13K) and phosphorylated Akt (pAkt) expression as well as enhancing natural killer (NK) cell activity. Taken together, our data strongly suggested that AEG-1 shRNA could block the carcinogenesis and progression of MHCC97-H cells and highlight the therapeutic potential of HP in HCC treatment, at least by part, by inhibiting the activation of the PI3K/Akt pathway and enhancing the NK cell-mediated immune response. These findings may provide a new strategy for HCC treatment.