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Article

Combination of metformin and sorafenib suppresses proliferation and induces autophagy of hepatocellular carcinoma via targeting the mTOR pathway

  • Authors:
    • Sunbin Ling
    • Lei Song
    • Ning Fan
    • Tingting Feng
    • Lu Liu
    • Xu Yang
    • Mingjie Wang
    • Yanling Li
    • Yu Tian
    • Feng Zhao
    • Ying Liu
    • Qihong Huang
    • Zhaoyuan Hou
    • Fei Xu
    • Lei Shi
    • Yan Li
  • View Affiliations / Copyright

    Affiliations: Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang 310003, P.R. China, The Second Affiliated Hospital of Dalian Medical University, Dalian, Liaoning 116023, P.R. China, Institute of Cancer Stem Cell, Dalian Medical University, Dalian, Liaoning 116044, P.R. China, Department of Intergrative Medicine, Zhejiang Cancer Hospital, Hangzhou, Zhejiang 310022, P.R. China, College of Basic Medical Sciences, Dalian Medical University, Dalian, Liaoning 116044, P.R. China
  • Pages: 297-309
    |
    Published online on: December 9, 2016
       https://doi.org/10.3892/ijo.2016.3799
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Abstract

The multi‑kinase inhibitor sorafenib is the only drug for which randomized control trials have shown improved patient survival in advanced hepatocellular carcinoma (HCC). However, life expectancy is extended in these cases by only a few months. The anti‑type II diabetes agent metformin was used in this study in an effort to find a more efficient approach to HCC treatment. Sorafenib effectively reversed the activation status of mTORC2 induced by metformin and enhanced the suppression of the mTORC1 and MAPK pathway by metformin in HCC cells, which may be responsible for reduced proliferation upon combined treatment. The metformin and sorafenib combination led to increased impaired proliferation and tumor inhibition of HCC in vitro and in vivo compared to single agent, which was partially bridged by disrupting the mTORC1/mTORC2 feedback loop. Metformin and sorafenib cooperated to promote apoptosis and autophagy in HCC cells. Pharmacological inhibition of autophagy sensitized HCC cells to metformin and sorefenib‑induced apoptotic cell death. Therefore, the anti‑autophagy treatment should be considered in metformin and sorafenib-based treatments in HCC cells.
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1 

Siegel R, Ma J, Zou Z and Jemal A: Cancer statistics, 2014. CA Cancer J Clin. 64:9–29. 2014. View Article : Google Scholar : PubMed/NCBI

2 

Jemal A, Bray F, Center MM, Ferlay J, Ward E and Forman D: Global cancer statistics. CA Cancer J Clin. 61:69–90. 2011. View Article : Google Scholar : PubMed/NCBI

3 

Perz JF, Armstrong GL, Farrington LA, Hutin YJ and Bell BP: The contributions of hepatitis B virus and hepatitis C virus infections to cirrhosis and primary liver cancer worldwide. J Hepatol. 45:529–538. 2006. View Article : Google Scholar : PubMed/NCBI

4 

Llovet JM, Ricci S, Mazzaferro V, Hilgard P, Gane E, Blanc JF, de Oliveira AC, Santoro A, Raoul JL, Forner A, et al SHARP Investigators Study Group: Sorafenib in advanced hepatocellular carcinoma. N Engl J Med. 359:378–390. 2008. View Article : Google Scholar : PubMed/NCBI

5 

Wilhelm SM, Adnane L, Newell P, Villanueva A, Llovet JM and Lynch M: Preclinical overview of sorafenib, a multikinase inhibitor that targets both Raf and VEGF and PDGF receptor tyrosine kinase signaling. Mol Cancer Ther. 7:3129–3140. 2008. View Article : Google Scholar : PubMed/NCBI

6 

Cheng AL, Kang YK, Chen Z, Tsao CJ, Qin S, Kim JS, Luo R, Feng J, Ye S, Yang TS, et al: Efficacy and safety of sorafenib in patients in the Asia-Pacific region with advanced hepatocellular carcinoma: A phase III randomised, double-blind, placebo-controlled trial. Lancet Oncol. 10:25–34. 2009. View Article : Google Scholar

7 

Lee MS, Hsu CC, Wahlqvist ML, Tsai HN, Chang YH and Huang YC: Type 2 diabetes increases and metformin reduces total, colorectal, liver and pancreatic cancer incidences in Taiwanese: A representative population prospective cohort study of 800,000 individuals. BMC Cancer. 11:202011. View Article : Google Scholar : PubMed/NCBI

8 

Chaiteerakij R, Yang JD, Harmsen WS, Slettedahl SW, Mettler TA, Fredericksen ZS, Kim WR, Gores GJ, Roberts RO, Olson JE, et al: Risk factors for intrahepatic cholangiocarcinoma: Association between metformin use and reduced cancer risk. Hepatology. 57:648–655. 2013. View Article : Google Scholar :

9 

Jalving M, Gietema JA, Lefrandt JD, de Jong S, Reyners AK, Gans RO and de Vries EG: Metformin: Taking away the candy for cancer? Eur J Cancer. 46:2369–2380. 2010. View Article : Google Scholar : PubMed/NCBI

10 

Donadon V, Balbi M, Mas MD, Casarin P and Zanette G: Metformin and reduced risk of hepatocellular carcinoma in diabetic patients with chronic liver disease. Liver Int. 30:750–758. 2010. View Article : Google Scholar : PubMed/NCBI

11 

Ling S, Feng T, Ke Q, Fan N, Li L, Li Z, Dong C, Wang C, Xu F, Li Y, et al: Metformin inhibits proliferation and enhances chemosensitivity of intrahepatic cholangiocarcinoma cell lines. Oncol Rep. 31:2611–2618. 2014.PubMed/NCBI

12 

Ling S, Tian Y, Zhang H, Jia K, Feng T, Sun D, Gao Z, Xu F, Hou Z, Li Y, et al: Metformin reverses multidrug resistance in human hepatocellular carcinoma Bel 7402/5 fluorouracil cells. Mol Med Rep. 10:2891–2897. 2014.PubMed/NCBI

13 

Chiou JF, Tai CJ, Wang YH, Liu TZ, Jen YM and Shiau CY: Sorafenib induces preferential apoptotic killing of a drug- and radio-resistant Hep G2 cells through a mitochondria-dependent oxidative stress mechanism. Cancer Biol Ther. 8:1904–1913. 2009. View Article : Google Scholar : PubMed/NCBI

14 

Klionsky DJ, Abdelmohsen K, Abe A, Abedin MJ, Abeliovich H, Acevedo Arozena A, Adachi H, Adams CM, Adams PD, Adeli K, et al: Guidelines for the use and interpretation of assays for monitoring autophagy (3rd edition). Autophagy. 12:1–222. 2016. View Article : Google Scholar : PubMed/NCBI

15 

Saito T, Chiba T, Yuki K, Zen Y, Oshima M, Koide S, Motoyama T, Ogasawara S, Suzuki E, Ooka Y, et al: Metformin, a diabetes drug, eliminates tumor-initiating hepatocellular carcinoma cells. PLoS One. 8:e700102013. View Article : Google Scholar : PubMed/NCBI

16 

Guo Z, Cao M, You A, Gao J, Zhou H, Li H, Cui Y, Fang F, Zhang W, Song T, et al: Metformin inhibits the pro-metastatic effect of Sorafenib in hepatocellular carcinoma by upregulating the expression of TIP30. Cancer Sci. 107:507–513. 2016. View Article : Google Scholar : PubMed/NCBI

17 

Anisimov VN: Metformin for cancer and aging prevention: Is it a time to make the long story short? Oncotarget. 6:39398–39407. 2015.PubMed/NCBI

18 

Kim JG, Lee SJ, Chae YS, Kang BW, Lee YJ, Oh SY, Kim MC, Kim KH and Kim SJ: Association between phosphorylated AMP-activated protein kinase and MAPK3/1 expression and prognosis for patients with gastric cancer. Oncology. 85:78–85. 2013. View Article : Google Scholar : PubMed/NCBI

19 

Martin M and Marais R: Braking BRAF: AMPK leaves ERK stranded in the desert. Mol Cell. 52:155–156. 2013. View Article : Google Scholar : PubMed/NCBI

20 

Baba Y, Nosho K, Shima K, Meyerhardt JA, Chan AT, Engelman JA, Cantley LC, Loda M, Giovannucci E, Fuchs CS, et al: Prognostic significance of AMP-activated protein kinase expression and modifying effect of MAPK3/1 in colorectal cancer. Br J Cancer. 103:1025–1033. 2010. View Article : Google Scholar : PubMed/NCBI

21 

Bhat M, Sonenberg N and Gores GJ: The mTOR pathway in hepatic malignancies. Hepatology. 58:810–818. 2013. View Article : Google Scholar : PubMed/NCBI

22 

Dibble CC, Asara JM and Manning BD: Characterization of Rictor phosphorylation sites reveals direct regulation of mTOR complex 2 by S6K1. Mol Cell Biol. 29:5657–5670. 2009. View Article : Google Scholar : PubMed/NCBI

23 

Liu P, Gan W, Inuzuka H, Lazorchak AS, Gao D, Arojo O, Liu D, Wan L, Zhai B, Yu Y, et al: Sin1 phosphorylation impairs mTORC2 complex integrity and inhibits downstream Akt signalling to suppress tumorigenesis. Nat Cell Biol. 15:1340–1350. 2013. View Article : Google Scholar : PubMed/NCBI

24 

Li QL, Gu FM, Wang Z, Jiang JH, Yao LQ, Tan CJ, Huang XY, Ke AW, Dai Z, Fan J, et al: Activation of PI3K/AKT and MAPK pathway through a PDGFRβ-dependent feedback loop is involved in rapamycin resistance in hepatocellular carcinoma. PLoS One. 7:e333792012. View Article : Google Scholar

25 

Wang C, Cigliano A, Delogu S, Armbruster J, Dombrowski F, Evert M, Chen X and Calvisi DF: Functional crosstalk between AKT/mTOR and Ras/MAPK pathways in hepatocarcinogenesis: Implications for the treatment of human liver cancer. Cell Cycle. 12:1999–2010. 2013. View Article : Google Scholar : PubMed/NCBI

26 

Yang H, Peng YF, Ni HM, Li Y, Shi YH, Ding WX and Fan J: Basal autophagy and feedback activation of Akt are associated with resistance to metformin-induced inhibition of hepatic tumor cell growth. PLoS One. 10:e01309532015. View Article : Google Scholar : PubMed/NCBI

27 

Gedaly R, Angulo P, Hundley J, Daily MF, Chen C, Koch A and Evers BM: PI-103 and sorafenib inhibit hepatocellular carcinoma cell proliferation by blocking Ras/Raf/MAPK and PI3K/AKT/mTOR pathways. Anticancer Res. 30:4951–4958. 2010.PubMed/NCBI

28 

Pignochino Y, Dell'Aglio C, Basiricò M, Capozzi F, Soster M, Marchiò S, Bruno S, Gammaitoni L, Sangiolo D, Torchiaro E, et al: The combination of sorafenib and everolimus abrogates mTORC1 and mTORC2 upregulation in osteosarcoma preclinical models. Clin Cancer Res. 19:2117–2131. 2013. View Article : Google Scholar : PubMed/NCBI

29 

Casadei Gardini A, Marisi G, Scarpi E, Scartozzi M, Faloppi L, Silvestris N, Masi G, Vivaldi C, Brunetti O, Tamberi S, et al: Effects of metformin on clinical outcome in diabetic patients with advanced HCC receiving sorafenib. Expert Opin Pharmacother. 16:2719–2725. 2015. View Article : Google Scholar : PubMed/NCBI

30 

Nicoletti F, Fagone P, Meroni P, McCubrey J and Bendtzen K: mTOR as a multifunctional therapeutic target in HIV infection. Drug Discov Today. 16:715–721. 2011. View Article : Google Scholar : PubMed/NCBI

31 

Jung CH, Ro SH, Cao J, Otto NM and Kim DH: mTOR regulation of autophagy. FEBS Lett. 584:1287–1295. 2010. View Article : Google Scholar : PubMed/NCBI

32 

Sun K, Guo XL, Zhao QD, Jing YY, Kou XR, Xie XQ, Zhou Y, Cai N, Gao L, Zhao X, et al: Paradoxical role of autophagy in the dysplastic and tumor-forming stages of hepatocarcinoma development in rats. Cell Death Dis. 4:e5012013. View Article : Google Scholar : PubMed/NCBI

33 

You A, Cao M, Guo Z, Zuo B, Gao J, Zhou H, Li H, Cui Y, Fang F, Zhang W, et al: Metformin sensitizes sorafenib to inhibit postoperative recurrence and metastasis of hepatocellular carcinoma in orthotopic mouse models. J Hematol Oncol. 9:202016. View Article : Google Scholar : PubMed/NCBI

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Copy and paste a formatted citation
Spandidos Publications style
Ling S, Song L, Fan N, Feng T, Liu L, Yang X, Wang M, Li Y, Tian Y, Zhao F, Zhao F, et al: Combination of metformin and sorafenib suppresses proliferation and induces autophagy of hepatocellular carcinoma via targeting the mTOR pathway. Int J Oncol 50: 297-309, 2017.
APA
Ling, S., Song, L., Fan, N., Feng, T., Liu, L., Yang, X. ... Li, Y. (2017). Combination of metformin and sorafenib suppresses proliferation and induces autophagy of hepatocellular carcinoma via targeting the mTOR pathway. International Journal of Oncology, 50, 297-309. https://doi.org/10.3892/ijo.2016.3799
MLA
Ling, S., Song, L., Fan, N., Feng, T., Liu, L., Yang, X., Wang, M., Li, Y., Tian, Y., Zhao, F., Liu, Y., Huang, Q., Hou, Z., Xu, F., Shi, L., Li, Y."Combination of metformin and sorafenib suppresses proliferation and induces autophagy of hepatocellular carcinoma via targeting the mTOR pathway". International Journal of Oncology 50.1 (2017): 297-309.
Chicago
Ling, S., Song, L., Fan, N., Feng, T., Liu, L., Yang, X., Wang, M., Li, Y., Tian, Y., Zhao, F., Liu, Y., Huang, Q., Hou, Z., Xu, F., Shi, L., Li, Y."Combination of metformin and sorafenib suppresses proliferation and induces autophagy of hepatocellular carcinoma via targeting the mTOR pathway". International Journal of Oncology 50, no. 1 (2017): 297-309. https://doi.org/10.3892/ijo.2016.3799
Copy and paste a formatted citation
x
Spandidos Publications style
Ling S, Song L, Fan N, Feng T, Liu L, Yang X, Wang M, Li Y, Tian Y, Zhao F, Zhao F, et al: Combination of metformin and sorafenib suppresses proliferation and induces autophagy of hepatocellular carcinoma via targeting the mTOR pathway. Int J Oncol 50: 297-309, 2017.
APA
Ling, S., Song, L., Fan, N., Feng, T., Liu, L., Yang, X. ... Li, Y. (2017). Combination of metformin and sorafenib suppresses proliferation and induces autophagy of hepatocellular carcinoma via targeting the mTOR pathway. International Journal of Oncology, 50, 297-309. https://doi.org/10.3892/ijo.2016.3799
MLA
Ling, S., Song, L., Fan, N., Feng, T., Liu, L., Yang, X., Wang, M., Li, Y., Tian, Y., Zhao, F., Liu, Y., Huang, Q., Hou, Z., Xu, F., Shi, L., Li, Y."Combination of metformin and sorafenib suppresses proliferation and induces autophagy of hepatocellular carcinoma via targeting the mTOR pathway". International Journal of Oncology 50.1 (2017): 297-309.
Chicago
Ling, S., Song, L., Fan, N., Feng, T., Liu, L., Yang, X., Wang, M., Li, Y., Tian, Y., Zhao, F., Liu, Y., Huang, Q., Hou, Z., Xu, F., Shi, L., Li, Y."Combination of metformin and sorafenib suppresses proliferation and induces autophagy of hepatocellular carcinoma via targeting the mTOR pathway". International Journal of Oncology 50, no. 1 (2017): 297-309. https://doi.org/10.3892/ijo.2016.3799
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