Antitumor effect of metformin on cholangiocarcinoma: In vitro and in vivo studies

Oncology Reports

Volumn 34, Issue 6, 2015, Pages 2987-2996

  Fujimori, Takayuki ^a   Kato, Kiyohito ^a   Fujihara, Shintaro ^a   Iwama, Hisakazu ^a   Yamashita, Takuma ^a   Kobayashi, Kiyoyuki ^a   Kamada, Hideki ^a   Morishita, Asahiro ^a   Kobara, Hideki ^a   Mori, Hirohito ^a   Okano, Keiichi ^a   Suzuki, Yasuyuki ^a   Masaki, Tsutomu ^a  

^a KAGAWA UNIVERSITY   (Japan)

Author keywords

Cell cycle; Cholangiocarcinoma; Cyclin D1; Metformin; MicroRNAs

Indexed keywords

ANAPLASTIC LYMPHOMA KINASE; CYCLIN D1; CYCLIN DEPENDENT KINASE 4; CYCLIN DEPENDENT KINASE INHIBITOR 1B; EPHRIN RECEPTOR; HYDROXYMETHYLGLUTARYL COENZYME A REDUCTASE KINASE; METFORMIN; MICRORNA; PEPTIDES AND PROTEINS; PROTEIN AX1; PROTEIN EPHA10; PROTEIN PYK; PROTEIN TYROSINE KINASE; RETINOBLASTOMA PROTEIN; UNCLASSIFIED DRUG; TUMOR PROTEIN;

ANIMAL EXPERIMENT; ANIMAL MODEL; ANTINEOPLASTIC ACTIVITY; ARTICLE; BILE DUCT CARCINOMA; CANCER CHEMOTHERAPY; CANCER GROWTH; CANCER INHIBITION; CELL CYCLE CHECKPOINT; CONTROLLED STUDY; DRUG MECHANISM; ENZYME ACTIVATION; G0 PHASE CELL CYCLE CHECKPOINT; HUMAN; HUMAN CELL; IN VITRO STUDY; IN VIVO STUDY; MALE; MOUSE; NONHUMAN; PRIORITY JOURNAL; PROTEIN EXPRESSION; PROTEIN PHOSPHORYLATION; ANIMAL; BIOSYNTHESIS; CELL PROLIFERATION; CHOLANGIOCARCINOMA; DIABETES MELLITUS, TYPE 2; DRUG EFFECTS; DRUG SCREENING; GENE EXPRESSION REGULATION;

ANIMALS; CELL PROLIFERATION; CHOLANGIOCARCINOMA; DIABETES MELLITUS, TYPE 2; GENE EXPRESSION REGULATION, NEOPLASTIC; HUMANS; METFORMIN; MICE; MICRORNAS; NEOPLASM PROTEINS; XENOGRAFT MODEL ANTITUMOR ASSAYS;

EID: 84943749410     PISSN: 1021335X     EISSN: 17912431     Source Type: Journal    
DOI: 10.3892/or.2015.4284     Document Type: Article

References (46)

1. Welzel TM, McGlynn KA, Hsing AW, O'Brien TR and Pfeiffer RM: Impact of classification of hilar cholangiocarcinomas (Klatskin tumors) on the incidence of intra-and extrahepatic cholangiocarcinoma in the United States. J Natl Cancer Inst 98: 873-875, 2006.
2. Khan SA, Davidson BR, Goldin RD, Heaton N, Karani J, Pereira SP, Rosenberg WM, Tait P, Taylor-Robinson SD, Thillainayagam AV, et al; British Society of Gastroenterology: Guidelines for the diagnosis and treatment of cholangiocarcinoma: An update. Gut 61: 1657-1669, 2012.
3. Everhart JE and Ruhl CE: Burden of digestive diseases in the United States Part III: Liver, biliary tract, and pancreas. Gastroenterology 136: 1134-1144, 2009.
4. Tyson GL and El-Serag HB: Risk factors for cholangiocarcinoma. Hepatology 54: 173-184, 2011.
5. Ben Sahra I, Laurent K, Loubat A, Giorgetti-Peraldi S, Colosetti P, Auberger P, Tanti JF, Le Marchand-Brustel Y and Bost F: The antidiabetic drug metformin exerts an antitumoral effect in vitro and in vivo through a decrease of cyclin D1 level. Oncogene 27: 3576-3586, 2008.
6. Libby G, Donnelly LA, Donnan PT, Alessi DR, Morris AD and Evans JM: New users of metformin are at low risk of incident cancer: A cohort study among people with type 2 diabetes. Diabetes Care 32: 1620-1625, 2009.
7. Landman GW, Kleefstra N, van Hateren KJ, Groenier KH, Gans RO and Bilo HJ: Metformin associated with lower cancer mortality in type 2 diabetes: ZODIAC-16. Diabetes Care 33: 322-326, 2010.
8. Kourelis TV and Siegel RD: Metformin and cancer: New applications for an old drug. Med Oncol 29: 1314-1327, 2012.
9. Anisimov VN, Egormin PA, Piskunova TS, Popovich IG, Tyndyk ML, Yurova MN, Zabezhinski MA, Anikin IV, Karkach AS and Romanyukha AA: Metformin extends life span of HER-2/neu transgenic mice and in combination with melatonin inhibits growth of transplantable tumors in vivo. Cell Cycle 9: 188-197, 2010.
10. Zhou XZ, Xue YM, Zhu B and Sha JP: Effects of metformin on proliferation of human colon carcinoma cell line SW-480. Nan Fang Yi Ke Da Xue Xue Bao 30: 1935-1938, 2010 (In Chinese).
11. Kato K, Gong J, Iwama H, Kitanaka A, Tani J, Miyoshi H, Nomura K, Mimura S, Kobayashi M, Aritomo Y, et al: The antidiabetic drug metformin inhibits gastric cancer cell proliferation in vitro and in vivo. Mol Cancer Ther 11: 549-560, 2012.
12. Kobayashi M, Kato K, Iwama H, Fujihara S, Nishiyama N, Mimura S, Toyota Y, Nomura T, Nomura K, Tani J, et al: Antitumor effect of metformin in esophageal cancer: In vitro study. Int J Oncol 42: 517-524, 2013.
13. Fujihara S, Kato K, Morishita A, Iwama H, Nishioka T, Chiyo T, Nishiyama N, Miyoshi H, Kobayashi M, Kobara H, et al: Antidiabetic drug metformin inhibits esophageal adenocarcinoma cell proliferation in vitro and in vivo. Int J Oncol 46: 2172-2180, 2015.
14. Miyoshi H, Kato K, Iwama H, Maeda E, Sakamoto T, Fujita K, Toyota Y, Tani J, Nomura T, Mimura S, et al: Effect of the anti-diabetic drug metformin in hepatocellular carcinoma in vitro and in vivo. Int J Oncol 45: 322-332, 2014.
15. Masaki T, Tokuda M, Yoshida S, Nakai S, Morishita A, Uchida N, Funaki T, Kita Y, Funakoshi F, Nonomura T, et al: Comparison study of the expressions of myristoylated alaninerich Ckinase substrate in hepatocellular carcinoma, liver cirrhosis, chronic hepatitis, and normal liver. Int J Oncol 26: 661-671, 2005.
16. Bradford MM: A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding. Anal Biochem 72: 248-254, 1976.
17. Laemmli UK: Cleavage of structural proteins during the assembly of the head of bacteriophage T4. Nature 227: 680-685, 1970.
18. Towbin H, Staehelin T and Gordon J: Electrophoretic transfer of proteins from polyacrylamide gels to nitrocellulose sheets: Procedure and some applications. Proc Natl Acad Sci USA 76: 4350-4354, 1979.
19. D'Incalci M, Colombo T, Ubezio P, Nicoletti I, Giavazzi R, Erba E, Ferrarese L, Meco D, Riccardi R, Sessa C, et al: The combination of yondelis and cisplatin is synergistic against human tumor xenografts. Eur J Cancer 39: 1920-1926, 2003.
20. Rizvi S and Gores GJ: Pathogenesis, diagnosis, and management of cholangiocarcinoma. Gastroenterology 145: 1215-1229, 2013.
21. DeOliveira ML, Cunningham SC, Cameron JL, Kamangar F, Winter JM, Lillemoe KD, Choti MA, Yeo CJ and Schulick RD: Cholangiocarcinoma: Thirty-one-year experience with 564 patients at a single institution. Ann Surg 245: 755-762, 2007.
22. Patel T: Increasing incidence and mortality of primary intrahepatic cholangiocarcinoma in the United States. Hepatology 33: 1353-1357, 2001.
23. Hezel AF and Zhu AX: Systemic therapy for biliary tract cancers. Oncologist 13: 415-423, 2008.
24. Bailey CJ and Turner RC: Metformin. NEngl J Med 334: 574-579, 1996.
25. Stang M, Wysowski DK and Butler-Jones D: Incidence of lactic acidosis in metformin users. Diabetes Care 22: 925-927, 1999.
26. Alimova IN, Liu B, Fan Z, Edgerton SM, Dillon T, Lind SE and Thor AD: Metformin inhibits breast cancer cell growth, colony formation and induces cell cycle arrest in vitro. Cell Cycle 8: 909-915, 2009.
27. Vazquez-Martin A, Oliveras-Ferraros C and Menendez JA: The antidiabetic drug metformin suppresses HER2 (erbB-2) oncoprotein overexpression via inhibition of the mTOR effector p70S6K1 in human breast carcinoma cells. Cell Cycle 8: 88-96, 2009.
28. Vázquez-Martín A, Oliveras-Ferraros C, del Barco S, Martin-Castillo B and Menéndez JA: mTOR inhibitors and the anti-diabetic biguanide metformin: New insights into the molecular management of breast cancer resistance to the HER2 tyrosine kinase inhibitor lapatinib (Tykerb). Clin Transl Oncol 11: 455-459, 2009.
29. 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.
30. Razumilava N and Gores GJ: Cholangiocarcinoma. Lancet 383: 2168-2179, 2014.
31. Franciosi M, Lucisano G, Lapice E, Strippoli GF, Pellegrini F and Nicolucci A: Metformin therapy and risk of cancer in patients with type 2 diabetes: Systematic review. PLoS One 8: e71583, 2013.
32. 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.
33. Masaki T, Shiratori Y, Rengifo W, Igarashi K, Yamagata M, Kurokohchi K, Uchida N, Miyauchi Y, Yoshiji H, Watanabe S, et al: Cyclins and cyclin-dependent kinases: Comparative study of hepatocellular carcinoma versus cirrhosis. Hepatology 37: 534-543, 2003.
34. Imamura K, Ogura T, Kishimoto A, Kaminishi M and Esumi H: Cell cycle regulation via p53 phosphorylation by a 5'-AMP activated protein kinase activator, 5-aminoimidazole-4-carboxamide-1-beta-D-ribofuranoside, in a human hepatocellular carcinoma cell line. Biochem Biophys Res Commun 287: 562-567, 2001.
35. Jones RG, Plas DR, Kubek S, Buzzai M, Mu J, Xu Y, Birnbaum MJ and Thompson CB: AMP-activated protein kinase induces a p53-dependent metabolic checkpoint. Mol Cell 18: 283-293, 2005.
36. Liang J, Shao SH, Xu ZX, Hennessy B, Ding Z, Larrea M, Kondo S, Dumont DJ, Gutterman JU, Walker CL, et al: The energy sensing LKB1-AMPK pathway regulates p27(kip1) phosphorylation mediating the decision to enter autophagy or apoptosis. Nat Cell Biol 9: 218-224, 2007.
37. Zhuang Y and Miskimins WK: Cell cycle arrest in metformin treated breast cancer cells involves activation of AMPK, downregulation of cyclin D1, and requires p27Kip1 or p21Cip1. J Mol Signal 3: 18, 2008.
38. Rocha GZ, Dias MM, Ropelle ER, Osório-Costa F, Rossato FA, Vercesi AE, Saad MJ and Carvalheira JB: Metformin amplifies chemotherapy-induced AMPK activation and antitumoral growth. Clin Cancer Res 17: 3993-4005, 2011.
39. Han S, Kim HY, Park K, Lee MS, Kim HJ and Kim YD: Expression of p27Kip1 and cyclin D1 proteins is inversely correlated and is associated with poor clinical outcome in human gastric cancer. J Surg Oncol 71: 147-154, 1999.
40. Aoyagi K, Koufuji K, Yano S, Murakami N, Terasaki Y, Yamasaki Y, Takeda J, Tanaka M and Shirouzu K: Immunohistochemical study on the expression of cyclin D1 and E in gastric cancer. Kurume Med J 47: 199-203, 2000.
41. Vazquez-Martin A, Oliveras-Ferraros C, Cufí S, Martin-Castillo B and Menendez JA: Metformin activates an ataxia telangiectasia mutated (ATM)/Chk2-regulated DNA damage-like response. Cell Cycle 10: 1499-1501, 2011.
42. Morishita A and Masaki T: miRNA in hepatocellular carcinoma. Hepatol Res 45: 128-141, 2015.
43. Barroso-del Jesus A, Lucena-Aguilar G and Menendez P: The miR-302-367 cluster as a potential stemness regulator in ESCs. Cell Cycle 8: 394-398, 2009.
44. Card DA, Hebbar PB, Li L, Trotter KW, Komatsu Y, Mishina Y and Archer TK: Oct4/Sox2-regulated miR-302 targets cyclin D1 in human embryonic stem cells. Mol Cell Biol 28: 6426-6438, 2008.
45. Yan GJ, Yu F, Wang B, Zhou HJ, Ge QY, Su J, Hu YL, Sun HX and Ding LJ: MicroRNA miR-302 inhibits the tumorigenicity of endometrial cancer cells by suppression of cyclin D1 and CDK1. Cancer Lett 345: 39-47, 2014.
46. Jiang X, Ma N, Wang D, Li F, He R, Li D, Zhao R, Zhou Q, Wang Y, Zhang F, et al: Metformin inhibits tumor growth by regulating multiple miRNAs in human cholangiocarcinoma. Oncotarget 6: 3178-3194, 2015.