Document Type: Review Article

Authors

1 Research Center for Pharmaceutical Nanotechnology, Biomedicine Institute, Tabriz University of Medical Sciences, Tabriz, Iran

2 Research Centre of Physiology, Faculty of Medicine, Semnan University of Medical Sciences, Semnan, Iran

10.33945/SAMI/IJABBR.2019.3.1

Abstract

Cancer -can significantly have ruining effects on very high of human beings, social, and economic condition. Gastrointestinal (GI) cancer has been reported as one of the most prevalent cancers and the incidence rates of this disorder is increasing across the world. This review explains practical recommendations for the management and improvement of patients with GI cancer by statins. Statins, a group of lipoproteins drugs, are used in medicine to treatment of lipid disorder, hypercholesterolemia reduction and cardiovascular risk. The exact mechanisms of anticancer activity of statins are still unknown. However, in some preclinical and epidemiological studies have reported them to have anticancer properties and therapeutic consequences for GI cancer based on preclinical evidence of their including antihypoxic processes, anti-invasive, induction of growth arrest and proapoptotic, radiosensitizing, angiogenesis and inhibition metastasis. The main objectives of this review paper are: 1. Explain the importance of sickness understanding and prognostic awareness in patients with cell proliferation, induction cell apoptosis, metastasis, angiogenesis, immunity and inflammatory GI cancers receiving statins groups. 2. Explain the importance of statins therapy in low- and middle- risk patients with GI cancers.

Keywords

Main Subjects

Agarwal, B, Bhendwal, S, Halmos, B, Moss, SF, Ramey, WG, Holt, PR. (1999). Lovastatin augments apoptosis induced by chemotherapeutic agents in colon cancer cells. Clin Cancer Res. 5:2223-2229.

Alexandre, L, Clark, AB, Bhutta, HY, Chan, SSM, Lewis, MPN, Hart, AR. (2016). Association Between Statin Use After Diagnosis of Esophageal Cancer and Survival: A Population-Based Cohort Study. Gastroenterol. 150:854-865. doi.org/10.1053/j.gastro.2015.12.039.

Assmus, B, Urbich, C, Aicher, A, Hofmann, WK, Haendeler, J, Rossig, L, Spyridopoulos, I, Zeiher, AM, Dimmeler, S. (2003). HMG-CoA reductase inhibitors reduce senescence and increase proliferation of endothelial progenitor cells via regulation of cell cycle regulatory genes. Circ Res. 92:1049-1055. doi:10.1161/01.RES.0000070067.64040.7C.

Bahrami, A, Amerizadeh, F, Hassanian, SM, ShahidSales, S, Khazaei, M, Maftouh, M, Ghayour-Mobarhan, M, Ferns, GA, Avan, A. (2017). Genetic variants as potential predictive biomarkers in advanced colorectal cancer patients treated with oxaliplatin-based chemotherapy. J Cell Physiol. 233(3):2193-2220.  doi:10.1002/jcp.25966.

Bayati Zadeh, J, Moradi kor, N, Olfati, A. (2015). The Effects of Different Levels Aqueous Extract of Fenugreek (Trigonella foenum-graecum L.) on Performance and Immune Response of Laying Hens. J Essential Oil Bearing Plants. 18(6):1476-1481, DOI: 10.1080/0972060X.2014.981594.

Beales, IL, Vardi, I, Dearman, L. (2012). Regular statin and aspirin use in patients with Barrett’s oesophagus is associated with a reduced incidence of oesophageal adenocarcinoma. Eur J Gastroenterol Hepatol. 24:917-923. doi: 10.1097/MEG.0b013e3283543f01.

Bhutta, HY, Alexandre, L, Clark, A, Holt, S, Lewis, MP, Hart, A. (2012). Mo1542 do statins prevent the histological subtypes of esophageal cancer? Prospective data from the UK General Practice Research Database (GPRD). Gastroenterol. 142:S-624.

Biswas, S, Criswell, TL, Wang, SE, Arteaga, CL. (2006). Inhibition of transforming growth factor-β signaling in human cancer: targeting a tumor suppressor network as a therapeutic strategy. Clin Cancer Res. 12:4142-4146.

Cardwell, CR, Hicks, BM, Hughes, C, Murray, LJ. (2014). Statin use after colorectal cancer diagnosis and survival: a populationbased cohort study. J Clin Oncol. 32:3177–3183.

Cao, Z, Fan-Minogue, H, Bellovin, DI, Yevtodiyenko, A, Arzeno, J, Yang, Q, Gambhir, SS, Felsher, DW. (2011). MYC phosphorylation, activation, and tumorigenic potential in hepatocellular carcinoma regulated by HMG-CoA reductase. Cancer Res. 71:2286–2297. doi:10.1158/0008-5472.CAN-10-3367.

 Chan KK, Oza AM, Siu LL. (2003). The Statins as Anticancer Agents. Clin Cancer Res. 9(1):10-9.

Cheng-Qian, Y, Xin-Jing, W, Wei-Xinbing, Zhuang-Lei G, Hong-Peng Z, Songde X, Pei-Lin W. (2014). Lovastatin inhibited the growth of gastric cancer cells. Hepatogastroenterol. 61:1-4. doi:10.1200/JCO.2013.54.4569.

Chiu, HF, Ho, SC, Chang, CC, Wu, TN, Yang, CY. (2011). Statins are associated with a reduced risk of gastric cancer: a population-based case-control study. Am J Gastroenterol. 106:2098–2103. doi:10.1038/ajg.2011.277.

Cress, RD, Morris, C, Ellison, GL, Goodman, MT. (2006). Secular changes in colorectal cancer incidence by subsite, stage at diagnosis, and race/ethnicity, 1992-2001. Cancer. 107(suppl 5):1142-1152. doi.org/10.1002/cncr.22011.

Chylack, LT Jr, Mantell, G, Wolfe, JK, Friend, J, Rosner, B. (1993). Lovastatin and the Korc, human lens; results of a two year study. Optom Vis Sci. 70:937-943.

De LLobet, LI, Baro, M, Mesia, R, Balart, J. (2014). Simvastatin enhances the effects of radiotherapy and cetuximab on a cell line (FaDu) derived from a squamous cell carcinoma of head and neck. Trans Oncol. 7:513–522. doi:10.1016/j.tranon.2014.02.008.

Demierre, MF, Higgins, PD, Gruber, SB, Hawk E, Lippman SM. (2005). Statins and cancer prevention. Nat Rev Cancer. 5:930–942. doi:10.1038/nrc1751.

Diakos Connie, I, Charles Kellie, A, McMillan Donald, C, Clarke Stephen, J. (2014). Cancer-related inflammation and treatment effectiveness. Lancet Oncol. 15(11):e493-503. doi:10.1016/S1470-2045(14)70263-3.

Edwards, BK, Ward, E, Kohler, BA, Eheman, C, Zauber, AG, Anderson, RN, Jemal, A, Schymura, MJ, Lansdorp-Vogelaar, I, Seeff, LC, van Ballegooijen, M, Goede, SL, Ries, LA. (2010). Annual report to the nation on the status of cancer, 1975-2006, featuring colorectal cancer trends and impact of interventions (risk factors, screening, and treatment) to reduce future rates. Cancer. 116:544-573. doi:10.1002/cncr.24760.

Emami, S, Olfati, A. (2017). Effects of Dietary Supplementing of Spirulina Platensis and Chlorella Vulgaris Microalgae on Hematologic Parameters in Streptozotocin- Induced Diabetic Rats. Iran J Ped Hematol Oncol. 7(3):163-170.

Farmer JA. (2000). Pleiotropic effects of statins. Curr Atherosclero Rep. 2:208–217. doi:10.1146/annurev.pharmtox.45.120403.095748.

Fildes, JE, Shaw, SM, Williams, SG. Yonan, N. (2009). Potential immunologic effects of statins in cancer following transplantation. Cancer Immunol Immunother. 58:461-467. doi:10.1007/s00262-008-0541-2.

Graaf, MR, Beiderbeck, AB, Egberts, AC, Richel, DJ, Guchelaar, HJ. (2004). The risk of cancer in users of statins. J Clin Oncol. 22:2388–2394. doi:10.1200/JCO.2004.02.027.

Graf, H, Jüngst, C, Straub, G, Dogan, S, Hoffmann, RT, Jakobs, T, Reiser, M, Waggershauser, T, Helmberger, T, Walter, A, Walli, A, Seidel, D, Goke, B, Jüngst D. (2008). Chemoembolization combined with pravastatin improves survival in patients with hepatocellular carcinoma. Digestion. 78:34–38. doi: 10.1159/000156702.

Guthrie, GJ, Roxburgh, CS, Horgan, PG, McMillan, DC. (2013). Does interleukin-6 link explain the link between tumour necrosis, local and systemic inflammatory responses and outcome in patients with colorectal cancer? Cancer Treat Rev. 39:89–96. 10.1016/j.ctrv.2012.07.003.

Habis, M, Wroblewski, K, Bradaric, M, Ismail, N, Yamada, SD, Litchfield, L, Lengyel, E, Romero, IL. (2014). Statin therapy is associated with improved survival in patients with non-serous-papillary epithelial ovarian cancer: a retrospective cohort analysis. PLoS One. 9:e104521.  doi:10.1371/journal.pone.0104521.

Haukka, J, San kila, R, Klaukka, T, Lonnqvist, J, Niskanen, L, Tanskanen, A, Wahlbeck, K, Tiihonen, J. (2010). Incidence of cancer and statin usage-record linkage study. Int J Cancer. 126:279–284. doi:10.1002/ijc.24536.

Jang, JJ, Ho, HK, Kwan, HH, Fajardo LF, Cooke JP. (2000). Angiogenesis is impaired by hypercholesterolemia: role of asymmetric dimethylarginine. Circulation. 102:1414–1419.

Jemal A, Bray F, Center MM, Ferlay J, Ward E, Forman D. (2011). Global cancer statistics. CA Cancer J Clin. 61:69–90. doi:10.3322/caac.20107. 

Joyce, JA, Pollard, JW. (2008). Microenvironmental regulation of metastasis. Nat Rev Cancer. 9:239–52. doi:10.1038/nrc2618.

Kato, S, Smalley, S, Sadarangani, A, Chen-Lin, K, Oliva, B, Brañes, J, Carvajal, J, Gejman, R, Owen, GI, Cuello, M. (2010). Lipophilic but not hydrophilic statins selectively induce cell death in gynaecological cancers expressing high levels of HMGCoA reductase. J Cell Mol Med. 14:1180–1193.  doi:10.1111/j.1582-4934.2009.00771.x.

Kawata, S, Yamasaki, E, Nagase, T, Inui, Y, Ito, N, Matsuda, Y, Inada, M, Tamura, S, Noda, S, Imai, Y, Matsuzawa, Y. (2001). Effect of pravastatin on survival in patients with advanced hepatocellular carcinoma. A randomized controlled trial. Br J Cancer. 84:886–91. doi:10.1054/bjoc.2000.1716.

Kenific, CM, Thorburn, A, Debnath, J. (2010). Autophagy and metastasis: another double-edged sword. Curr Opinion Cell Biol. 22:241–5.  doi:10.1016/j.ceb.2009.10.008. 

Kim, WS, Kim, MM, Choi, HJ, Yoon, SS, Lee, MH, Park, K, Park, CH, Kang, WK. (2001). Phase II study of high-dose lovastatin in patients with advanced gastric adenocarcinoma. Invest New Drugs. 19:81–83.

Korc, M, Friesel, RE. (2009). The role of fibroblast growth factors in tumor growth. Curr Cancer Drug Targets. 5:639-651.

Kureishi, Y, Luo, Z, Shiojima, I, Bialik A, Fulton D, Lefer DJ, Sessa WC, Walsh K. (2000). The HMG-CoA reductase inhibitor simvastatin activates the protein kinase akt and promotes angiogenesis in normocholesterolemic animals. Nat Med. 6:1004–1010. doi:10.1038/79510.

LaRosa JC. (2001). Pleiotropic effects of statins and their clinical significance. Am J Cardiol. 88:291–293.

Lee, SJ, Lee, I, Lee, J, Park, C, Kang, WK. (2014). Statins, 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors, potentiate the anti-angiogenic effects of bevacizumab by suppressing angiopoietin2, BiP, and Hsp90a in human colorectal cancer. Br J Cancer. 111(3):497-505. doi:10.1038/bjc.

Lee, J, Lee, I, Park, C, Kang, WK.  (2006). Lovastatin-induced RhoA modulation and its effect on senescence in prostate cancer cells. Biochem Biophys Res Commun. 339:748–754. doi:10.1016/j.bbrc.2005.11.075.

Nielsen SF, Nordestgaard BG, Bojesen SE. (2012). Statin use and reduced cancer-related mortality. N Engl J Med. 367:1792–1802.

Ogunwobi, OO, Beales, IL. (2008). Statins inhibit proliferation and induce apoptosis in Barrett’s esophageal adenocarcinoma cells. Am J Gastroenterol. 103:825–837. doi:10.1111/j.1572-0241.2007.01773.x.

Olfati, A, Moghaddam, G, Rafat Khafar, K, Mojtahedin, A, Abdolahzadeh, A. (2018). Role of follicle-stimulating hormone and estradiol benzoate in recovering spermatogenesis in tamoxifen-injured rats. Asian Pacific J Reprod. 7(6):248-253. doi: 10.4103/2305-0500.246342.

Pahan, K. (2006). Lipid-lowering drugs. Cell Mol Life Sci. 63:1165-1178. doi:10.1007/s00018-005-5406-7.

Park, C, Lee, I, Kang, WK. (2001). Lovastatin-induced E2F-1 modulation and its effect on prostate cancer cell death. Carcinogenesis. 22:1727–1731.

Pedersen, TR, Wilhelmsen, L, Faergeman, O, Strandberg, TE, Thorgeirsson, G, Troedsson, L, Kristianson, J, Berg, K, Cook, TJ, Haghfelt, T, Kjekshus, J, Miettinen, T, Olsson, AG, Pyörälä, K, Wedel, H. (2000). Follow-up study of patients randomized in the Scandinavian Simvastatin Survival Study (4S) of cholesterol lowering. Am J Cardiol. 86:257–262.

Pisanti S, Picardi P, Ciaglia E, D''Alessandro A, Bifulco M. (2014). Novel prospects of statins as therapeutic agents in cancer. Pharmacol Res. 88:84-98. doi:10.1016/j.phrs.2014.06.013.

Poggi, A, Musso, A, Boero, S, Canevali, P, Zocchi Maria, R. (2010). Statins as Either Immunomodulators or Anti-Cancer Drugs: Functional Activities on Tumor Stromal Cells and Natural Killer Cells. Anti-Inflammatory & Anti-Allergy Agents in Medicinal Chemistry. 9:82-92. doi:10.2174/187152310790711719.

Putoczki, TL, Thiem, S, Loving, A, Busuttil, RA, Wilson, NJ, Ziegler, PK, Nguyen, PM, Preaudet, A, Farid, R, Edwards, KM, Boglev, Y, Luwor, RB, Jarnicki, A, Horst, D, Boussioutas, A, Heath, JK, Sieber, OM, Pleines, I, Kile, BT, Nash, A, Greten, FR, McKenzie, BS, Ernst, M. (2013). Interleukin-11 is the dominant IL-6 family cytokine during gastrointestinal tumorigenesis and can be targeted therapeutically. Cancer Cell. 24:257–71. doi:10.1016/j.ccr.2013.06.017.

Siegel Rebecca, L, Miller Kimberly, D,  Ahmedin, J. (2018). Cancer Statistics. 2018. Ca Cancer J Clin. 68:7–30. doi:10.3322/caac.21442.

Siegel, RL, Ward, EM, Jemal, A. (2012). Trends in colorectal cancer incidence rates in the United States by tumor location and stage, 1992-2008. Cancer Epidemiol Biomarkers Prev. 21:411-416.

Singh, PP, Singh, S. (2013). Statins are associated with reduced risk of gastric cancer: a systematic review and meta-analysis. An Oncol. 24:1721–1730. doi:10.1093/annonc/mdt150.

Spampanato, C, De Maria, S, Sarnataro, M, Giordano, E, Zanfardino, M, Baiano, S, Cartenì, M, Morelli, F. (2012). Simvastatin inhibits cancer cell growth by inducing apoptosis correlated to activation of Bax and down-regulation of BCL-2 gene expression. Int J Oncol. 40:935–41.

Spyridopoulos, I, Haendeler, J, Urbich, C, Brummendorf, TH, Oh, H, Schneider, MD, Zeiher, AM, Dimmeler, S. (2004). Statins enhance migratory capacity by upregulation of the telomere repeat-binding factor TRF2 in endothelial progenitor cells. Circulation. 110:3136–3142. doi:10.1161/01.CIR.0000142866.50300.EB.

Wang, W, Collie-Duguid, E, Cassidy, J. (2002). Cerivastatin enhances the cytotoxicity of 5-fluorouracil on chemosensitive and resitant colorectal cancer cell lines. FEBS Lett. 531:415–420.

Weis, M, Heeschen, C, Glassford, AJ, Cooke, JP. (2002). Statins Have Biphasic Effects on Angiogenesis. Circulation. 105:739-745.

Weeks, JC, Catalano, PJ, Cronin, A, Finkelman, MD, Mack, JW, Nancy L. Keating, NL, Schrag, D. (2012). Patients’ expectations about effects of chemotherapy for advanced cancer. N Engl J Med. 367:1616-1625.

WHO.  Latest world cancer statistics Global cancer burden rises to 14.1 million new cases in 2012: Marked increase in breast cancers must be addressed. 2013.

Yang, Z, Yang, D, Xie, L, Sun, Y, Huang, Y, Sun, H, Liu, P, Wu, Z. (2009).  Treatment of metastatic spinal tumors by percutaneous vertebroplasty versus percutaneous vertebroplasty combined with interstitial implantation of 125I seeds. Acta Radiologica. 50:1142–8.

Ye F, Zhang GH, Guan BX, Xu, XC. (2012). Suppression of esophageal cancer cell growth using curcumin, (-)-epigallocatechin-3-gallate and lovastatin. World J Gastroenterol. 18:126–135. doi:10.3748/wjg.v18.i2.126.