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Article

Propofol inhibits hepatocellular carcinoma growth and invasion through the HMGA2‑mediated Wnt/β‑catenin pathway

  • Authors:
    • Wei Ou
    • Jie Lv
    • Xiaohua Zou
    • Yin Yao
    • Jinli Wu
    • Jian Yang
    • Zhumei Wang
    • Yan Ma
  • View Affiliations / Copyright

    Affiliations: Department of Anesthesiology, The Affiliated Hospital of Guizhou Medical University, Guizhou, Guiyang 550001, P.R. China
  • Pages: 2501-2506
    |
    Published online on: March 22, 2017
       https://doi.org/10.3892/etm.2017.4253
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Abstract

Propofol is a commonly used intravenous anesthetic in tumor surgery. Recently, studies have confirmed that propofol has an antitumor effect on hepatocellular carcinoma (HCC); however, the molecular mechanism underlying this effect has not been elucidated until now. The present study aimed to investigate the mechanism of propofol on HepG2 cell proliferation, apoptosis and invasion, focusing on High Mobility Group AT‑Hook 2 (HMGA2)‑mediated Wnt/β‑catenin pathway. The HepG2 cells were treated with various concentrations of propofol for 24 h, the relative protein levels of HMGA2, Wnt3a, β‑catenin, Snail Family Zinc Finger 1 and c‑myc were determined by western blot analysis. HMGA2‑pcDNA3.1 plasmid was transfected into the HepG2 cells to overexpress HMGA2. Cell proliferation, apoptosis and invasion were examined by MTT assays, flow cytometry and Transwell‑matrigel invasion assays, respectively. The results showed that propofol suppressed HMGA2 expression and Wnt/β‑catenin signaling in a dose‑dependent manner. Propofol was able to inhibit cell proliferation and invasion, and induce cell apoptosis of HepG2 cells; however, these effects were attenuated by HMGA2 overexpression. The suppressed Wnt/β‑catenin signaling in HepG2 cells by treatment with propofol was also reversed by HMGA2 overexpression. In conclusion, this study provided a novel mechanism underlying the anti‑tumor function of propofol on HCC. To the best of our knowledge, the present study is the first to demonstrate that propofol could downregulate the expression of HMGA2, which inhibited the Wnt/β‑catenin pathway, thus leading to the inhibition of cell proliferation and invasion, as well as the apoptosis of HepG2 cells.
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1 

Gomes MA, Priolli DG, Tralhão JG and Botelho MF: Hepatocellular carcinoma: Epidemiology, biology, diagnosis, and therapies. Rev Assoc Med Bras. 1992.59:514–524. 2013. View Article : Google Scholar

2 

Herszényi L and Tulassay Z: Epidemiology of gastrointestinal and liver tumors. Eur Rev Med Pharmacol Sci. 14:249–258. 2010.PubMed/NCBI

3 

Ribatti D, Vacca A, Nico B, Sansonno D and Dammacco F: Angiogenesis and anti-angiogenesis in hepatocellular carcinoma. Cancer Treat Rev. 32:437–444. 2006. View Article : Google Scholar : PubMed/NCBI

4 

Pang RW and Poon RT: From molecular biology to targeted therapies for hepatocellular carcinoma: The future is now. Oncology. 72 Suppl 1:S30–S44. 2007. View Article : Google Scholar

5 

Castroagudín JF, Delgado M, Villanueva A, Bustamante M, Martínez J, Otero E, Tomé S, Martínez SM, Segade FR, Conde R, et al: Safety of percutaneous ethanol injection as neoadjuvant therapy for hepatocellular carcinoma in waiting list liver transplant candidates. Transplant Proc. 37:3871–3873. 2005. View Article : Google Scholar : PubMed/NCBI

6 

Gluer AM, Cocco N, Laurence JM, Johnston ES, Hollands MJ, Pleass HC, Richardson AJ and Lam VW: Systematic review of actual 10-year survival following resection for hepatocellular carcinoma. HPB (Oxford). 14:285–290. 2012. View Article : Google Scholar : PubMed/NCBI

7 

Zhou XD: Recurrence and metastasis of hepatocellular carcinoma: Progress and prospects. Hepatobiliary Pancreat Dis Int. 1:35–41. 2002.PubMed/NCBI

8 

Altenburg JD, Harvey KA, McCray S, Xu Z and Siddiqui RA: A novel 2,6-diisopropylphenyl-docosahexaenoamide conjugate induces apoptosis in T cell acute lymphoblastic leukemia cell lines. Biochem Biophys Res Commun. 411:427–432. 2011. View Article : Google Scholar : PubMed/NCBI

9 

Mammoto T, Mukai M, Mammoto A, Yamanaka Y, Hayashi Y, Mashimo T, Kishi Y and Nakamura H: Intravenous anesthetic, propofol inhibits invasion of cancer cells. Cancer Lett. 184:165–170. 2002. View Article : Google Scholar : PubMed/NCBI

10 

Miao Y, Zhang Y, Wan H, Chen L and Wang F: GABA-receptor agonist, propofol inhibits invasion of colon carcinoma cells. Biomed Pharmacother. 64:583–588. 2010. View Article : Google Scholar : PubMed/NCBI

11 

Wang ZT, Gong HY, Zheng F, Liu DJ and Dong TL: Propofol suppresses proliferation and invasion of pancreatic cancer cells by upregulating microRNA-133a expression. Genet Mol Res. 14:7529–7537. 2015. View Article : Google Scholar : PubMed/NCBI

12 

Wang ZT, Gong HY, Zheng F, Liu DJ and Yue XQ: Propofol suppresses proliferation and invasion of gastric cancer cells via downregulation of microRNA-221 expression. Genet Mol Res. 14:8117–8124. 2015. View Article : Google Scholar : PubMed/NCBI

13 

Zhang J, Zhang D, Wu GQ, Feng ZY and Zhu SM: Propofol inhibits the adhesion of hepatocellular carcinoma cells by upregulating microRNA-199a and downregulating MMP-9 expression. Hepatobiliary Pancreat Dis Int. 12:305–309. 2013. View Article : Google Scholar : PubMed/NCBI

14 

Zhang J, Wu GQ, Zhang Y, Feng ZY and Zhu SM: Propofol induces apoptosis of hepatocellular carcinoma cells by upregulation of microRNA-199a expression. Cell Biol Int. 37:227–232. 2013. View Article : Google Scholar : PubMed/NCBI

15 

Zhang J, Shan WF, Jin TT, Wu GQ, Xiong XX, Jin HY and Zhu SM: Propofol exerts anti-hepatocellular carcinoma by microvesicle-mediated transfer of miR-142-3p from macrophage to cancer cells. J Transl Med. 12:2792014. View Article : Google Scholar : PubMed/NCBI

16 

Morishita A, Zaidi MR, Mitoro A, Sankarasharma D, Szabolcs M, Okada Y, D'Armiento J and Chada K: HMGA2 is a driver of tumor metastasis. Cancer Res. 73:4289–4299. 2013. View Article : Google Scholar : PubMed/NCBI

17 

Lee CT, Zhang L, Mounajjed T and Wu TT: High mobility group AT-hook 2 is overexpressed in hepatoblastoma. Hum Pathol. 44:802–810. 2013. View Article : Google Scholar : PubMed/NCBI

18 

Marijon H, Dokmak S, Paradis V, Zappa M, Bieche I, Bouattour M, Raymond E and Faivre S: Epithelial-to-mesenchymal transition and acquired resistance to sunitinib in a patient with hepatocellular carcinoma. J Hepatol. 54:1073–1078. 2011. View Article : Google Scholar : PubMed/NCBI

19 

Tan EJ, Thuault S, Caja L, Carletti T, Heldin CH and Moustakas A: Regulation of transcription factor Twist expression by the DNA architectural protein high mobility group A2 during epithelial-to-mesenchymal transition. J Biol Chem. 287:7134–7145. 2012. View Article : Google Scholar : PubMed/NCBI

20 

Thuault S, Tan EJ, Peinado H, Cano A, Heldin CH and Moustakas A: HMGA2 and Smads co-regulate SNAIL1 expression during induction of epithelial-to-mesenchymal transition. J Biol Chem. 283:33437–33446. 2008. View Article : Google Scholar : PubMed/NCBI

21 

Zha L, Zhang J, Tang W, Zhang N, He M, Guo Y and Wang Z: HMGA2 elicits EMT by activating the Wnt/β-catenin pathway in gastric cancer. Dig Dis Sci. 58:724–733. 2013. View Article : Google Scholar : PubMed/NCBI

22 

Tsuchiya M, Asada A, Arita K, Utsumi T, Yoshida T, Sato EF, Utsumi K and Inoue M: Induction and mechanism of apoptotic cell death by propofol in HL-60 cells. Acta Anaesthesiol Scand. 46:1068–1074. 2002. View Article : Google Scholar : PubMed/NCBI

23 

Inada T, Kubo K and Shingu K: Possible link between cyclooxygenase-inhibiting and antitumor properties of propofol. J Anesth. 25:569–575. 2011. View Article : Google Scholar : PubMed/NCBI

24 

Su Z, Hou XK and Wen QP: Propofol induces apoptosis of epithelial ovarian cancer cells by upregulation of microRNA let-7i expression. Eur J Gynaecol Oncol. 35:688–691. 2014.PubMed/NCBI

25 

Ye Z, Jingzhong L, Yangbo L, Lei C and Jiandong Y: Propofol inhibits proliferation and invasion of osteosarcoma cells by regulation of microRNA-143 expression. Oncol Res. 21:201–207. 2013. View Article : Google Scholar : PubMed/NCBI

26 

Zhou X, Benson KF, Ashar HR and Chada K: Mutation responsible for the mouse pygmy phenotype in the developmentally regulated factor HMGI-C. Nature. 376:771–774. 1995. View Article : Google Scholar : PubMed/NCBI

27 

Langelotz C, Schmid P, Jakob C, Heider U, Wernecke KD, Possinger K and Sezer O: Expression of high-mobility-group-protein HMGI-C mRNA in the peripheral blood is an independent poor prognostic indicator for survival in metastatic breast cancer. Br J Cancer. 88:1406–1410. 2003. View Article : Google Scholar : PubMed/NCBI

28 

Wang X, Liu X, Li AY, Chen L, Lai L, Lin HH, Hu S, Yao L, Peng J, Loera S, et al: Overexpression of HMGA2 promotes metastasis and impacts survival of colorectal cancers. Clin Cancer Res. 17:2570–2580. 2011. View Article : Google Scholar : PubMed/NCBI

29 

Sarhadi VK, Wikman H, Salmenkivi K, Kuosma E, Sioris T, Salo J, Karjalainen A, Knuutila S and Anttila S: Increased expression of high mobility group A proteins in lung cancer. J Pathol. 209:206–212. 2006. View Article : Google Scholar : PubMed/NCBI

30 

Wu L, Wang Z, Lu R and Jiang W: Expression of high mobility group A2 is associated with poor survival in hepatocellular carcinoma. Pathol Oncol Res. 18:983–987. 2012. View Article : Google Scholar : PubMed/NCBI

31 

Gupta A, Verma A, Mishra AK, Wadhwa G, Sharma SK and Jain CK: The Wnt pathway: Emerging anticancer strategies. Recent Pat Endocr Metab Immune Drug Discov. 7:138–147. 2013. View Article : Google Scholar : PubMed/NCBI

32 

Rosenbluh J, Wang X and Hahn WC: Genomic insights into WNT/β-catenin signaling. Trends Pharmacol Sci. 35:103–109. 2014. View Article : Google Scholar : PubMed/NCBI

33 

Dai C, Stolz DB, Kiss LP, Monga SP, Holzman LB and Liu Y: Wnt/beta-catenin signaling promotes podocyte dysfunction and albuminuria. J Am Soc Nephrol. 20:1997–2008. 2009. View Article : Google Scholar : PubMed/NCBI

34 

Breuhahn K, Longerich T and Schirmacher P: Dysregulation of growth factor signaling in human hepatocellular carcinoma. Oncogene. 25:3787–3800. 2006. View Article : Google Scholar : PubMed/NCBI

35 

Baulida J and García de Herreros A: Snail1-driven plasticity of epithelial and mesenchymal cells sustains cancer malignancy. Biochim Biophys Acta. 1856:55–61. 2015.PubMed/NCBI

36 

Vita M and Henriksson M: The Myc oncoprotein as a therapeutic target for human cancer. Semin Cancer Biol. 16:318–330. 2006. View Article : Google Scholar : PubMed/NCBI

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Copy and paste a formatted citation
Spandidos Publications style
Ou W, Lv J, Zou X, Yao Y, Wu J, Yang J, Wang Z and Ma Y: Propofol inhibits hepatocellular carcinoma growth and invasion through the HMGA2‑mediated Wnt/β‑catenin pathway. Exp Ther Med 13: 2501-2506, 2017.
APA
Ou, W., Lv, J., Zou, X., Yao, Y., Wu, J., Yang, J. ... Ma, Y. (2017). Propofol inhibits hepatocellular carcinoma growth and invasion through the HMGA2‑mediated Wnt/β‑catenin pathway. Experimental and Therapeutic Medicine, 13, 2501-2506. https://doi.org/10.3892/etm.2017.4253
MLA
Ou, W., Lv, J., Zou, X., Yao, Y., Wu, J., Yang, J., Wang, Z., Ma, Y."Propofol inhibits hepatocellular carcinoma growth and invasion through the HMGA2‑mediated Wnt/β‑catenin pathway". Experimental and Therapeutic Medicine 13.5 (2017): 2501-2506.
Chicago
Ou, W., Lv, J., Zou, X., Yao, Y., Wu, J., Yang, J., Wang, Z., Ma, Y."Propofol inhibits hepatocellular carcinoma growth and invasion through the HMGA2‑mediated Wnt/β‑catenin pathway". Experimental and Therapeutic Medicine 13, no. 5 (2017): 2501-2506. https://doi.org/10.3892/etm.2017.4253
Copy and paste a formatted citation
x
Spandidos Publications style
Ou W, Lv J, Zou X, Yao Y, Wu J, Yang J, Wang Z and Ma Y: Propofol inhibits hepatocellular carcinoma growth and invasion through the HMGA2‑mediated Wnt/β‑catenin pathway. Exp Ther Med 13: 2501-2506, 2017.
APA
Ou, W., Lv, J., Zou, X., Yao, Y., Wu, J., Yang, J. ... Ma, Y. (2017). Propofol inhibits hepatocellular carcinoma growth and invasion through the HMGA2‑mediated Wnt/β‑catenin pathway. Experimental and Therapeutic Medicine, 13, 2501-2506. https://doi.org/10.3892/etm.2017.4253
MLA
Ou, W., Lv, J., Zou, X., Yao, Y., Wu, J., Yang, J., Wang, Z., Ma, Y."Propofol inhibits hepatocellular carcinoma growth and invasion through the HMGA2‑mediated Wnt/β‑catenin pathway". Experimental and Therapeutic Medicine 13.5 (2017): 2501-2506.
Chicago
Ou, W., Lv, J., Zou, X., Yao, Y., Wu, J., Yang, J., Wang, Z., Ma, Y."Propofol inhibits hepatocellular carcinoma growth and invasion through the HMGA2‑mediated Wnt/β‑catenin pathway". Experimental and Therapeutic Medicine 13, no. 5 (2017): 2501-2506. https://doi.org/10.3892/etm.2017.4253
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