Giảm Biểu Thị Survivin Làm Giảm Hiệu Quả Điều Trị Curcumin Trong Các Tế Bào Ung Thư Gan

Annals of Surgical Oncology - Tập 19 - Trang 3547-3555 - 2012
Chin-Sheng Hung1,2,3,4, Hui-Hsiung Liu5, Ming-Te Huang1,2,3,6, Chao-Wen Cheng1, Li-Jen Kuo1,2,3,4, Yuan-Soon Ho7,8, Chih-Hsiung Wu1,2,3,6, Chien-Ming Chen8, Po-Li Wei1,2,3,4, Yu-Jia Chang1,2,3,4,7
1Graduate Institute of Clinical Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan
2Department of Surgery, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan
3Division of General Surgery, Department of Surgery, Taipei Medical University Hospital, Taipei Medical University, Taipei, Taiwan
4Cancer Research Center, Taipei Medical University Hospital, Taipei Medical University, Taipei, Taiwan
5Department of Public Health, School of Public Health, Taipei Medical University, Taiwan, Taipei, Taiwan
6Division of General Surgery, Department of Surgery, Shuang Ho Hospital, Taipei Medical University, Taipei, Taiwan
7Center of Excellence for Cancer Research, Taipei Medical University, Taipei, Taiwan
8School of Medical Laboratory Science and Biotechnology, College of Medical Science and Technology, Taipei Medical University, Taipei, Taiwan

Tóm tắt

Survivin là một mục tiêu điều trị tiềm năng cho ung thư. Việc gia tăng biểu hiện survivin thúc đẩy sự sống sót của tế bào và khả năng kháng điều trị. Tuy nhiên, có rất ít thông tin về việc mức độ biểu hiện của survivin ảnh hưởng như thế nào đến việc điều trị curcumin trong ung thư tế bào gan (HCC). Biểu hiện survivin đã bị ức chế trong các tế bào HCC bằng cách sử dụng kỹ thuật RNA can thiệp ngắn (siRNA). Các hiệu ứng chống ung thư của curcumin đã được kiểm tra bằng hệ thống cảm biến sinh học, thử nghiệm MTT, thử nghiệm TUNEL và phân tích chu kỳ tế bào. Kháng curcumin phát triển trong các tế bào có biểu hiện survivin bị ức chế, ngược lại với các tế bào mẹ, như được xác định bởi các thử nghiệm sống sót. Phân tích chu kỳ tế bào và thử nghiệm TUNEL cho thấy rằng phần trăm tế bào chết qua quá trình apoptosis tăng lên trong các tế bào bị ức chế siRNA so với các tế bào siRNA survivin. Việc ức chế biểu hiện survivin dẫn đến kháng curcumin thông qua việc điều chỉnh biểu hiện của Bcl-2 và Bax. Chúng tôi kết luận rằng mức độ biểu hiện của survivin có thể điều hòa hiệu quả điều trị của curcumin trong các tế bào HCC.

Từ khóa

#Survivin #curcumin #ung thư tế bào gan #RNA can thiệp ngắn #kháng điều trị

Tài liệu tham khảo

Bruix J, Boix L, Sala M, Llovet JM. Focus on hepatocellular carcinoma. Cancer Cell. 2004;5:215–9. Llovet JM, Burroughs A, Bruix J. Hepatocellular carcinoma. Lancet. 2003;362:1907–17. Thomas MB, Zhu AX. Hepatocellular carcinoma: the need for progress. J Clin Oncol. 2005;23:2892–9. Bruix J, Llovet JM. Major achievements in hepatocellular carcinoma. Lancet. 2009;373:614–6. Ambrosini G, Adida C, Altieri DC. A novel anti-apoptosis gene, survivin, expressed in cancer and lymphoma. Nat Med. 1997;3:917–21. Reed JC. The survivin saga goes in vivo. J Clin Invest. 2001;108:965–9. Li F, Ambrosini G, Chu EY, Plescia J, Tognin S, Marchisio PC, et al. Control of apoptosis and mitotic spindle checkpoint by survivin. Nature. 1998;396:580–4. Chandele A, Prasad V, Jagtap JC, Shukla R, Shastry PR. Upregulation of survivin in G2/M cells and inhibition of caspase 9 activity enhances resistance in staurosporine-induced apoptosis. Neoplasia. 2004;6:29–40. Fields AC, Cotsonis G, Sexton D, Santoianni R, Cohen C. Survivin expression in hepatocellular carcinoma: correlation with proliferation, prognostic parameters, and outcome. Mod Pathol. 2004;17:1378–85. Augello C, Caruso L, Maggioni M, Donadon M, Montorsi M, Santambrogio R, et al. Inhibitors of apoptosis proteins (IAPs) expression and their prognostic significance in hepatocellular carcinoma. BMC Cancer. 2009;9:125. Huang MT, Wei PL, Liu JJ, Liu DZ, Huey-Chun H, An J, et al. Knockdown of thrombomodulin enhances HCC cell migration through increase of ZEB1 and decrease of E-cadherin gene expression. Ann Surg Oncol. 2010;17:3379–85. Zhang T, Ding X, Wei D, Cheng P, Su X, Liu H, et al. Sorafenib improves the survival of patients with advanced hepatocellular carcinoma: a meta-analysis of randomized trials. Anticancer Drugs. 2010;21:326–32. Aoki Y, Feldman GM, Tosato G. Inhibition of STAT3 signaling induces apoptosis and decreases survivin expression in primary effusion lymphoma. Blood. 2003;101:1535–42. Kanda N, Seno H, Konda Y, Marusawa H, Kanai M, Nakajima T, et al. STAT3 is constitutively activated and supports cell survival in association with survivin expression in gastric cancer cells. Oncogene. 2004;23:4921–9. Fuke H, Shiraki K, Sugimoto K, Tanaka J, Beppu T, Yoneda K, et al. Jak inhibitor induces S phase cell-cycle arrest and augments TRAIL-induced apoptosis in human hepatocellular carcinoma cells. Biochem Biophys Res Commun. 2007;363:738–44. Anand P, Sundaram C, Jhurani S, Kunnumakkara AB, Aggarwal BB. Curcumin and cancer: an “old-age” disease with an “age-old” solution. Cancer Lett. 2008;267:133–64. Shishodia S, Singh T, Chaturvedi MM. Modulation of transcription factors by curcumin. Adv Exp Med Biol. 2007;595:127–48. Ravindran J, Prasad S, Aggarwal BB. Curcumin and cancer cells: how many ways can curry kill tumor cells selectively? AAPS J. 2009;11:495–510. Johnson JJ, Mukhtar H. Curcumin for chemoprevention of colon cancer. Cancer Lett. 2007;255:170–81. Glienke W, Maute L, Wicht J, Bergmann L. Curcumin inhibits constitutive STAT3 phosphorylation in human pancreatic cancer cell lines and downregulation of survivin/BIRC5 gene expression. Cancer Invest. 2010;28:166–71. Chang YJ, Tai CJ, Kuo LJ, Wei PL, Liang HH, Liu TZ, et al. Glucose-regulated protein 78 (GRP78) mediated the efficacy to curcumin treatment on hepatocellular carcinoma. Ann Surg Oncol. 2011;18:2395–403. Chang YJ, Chiu CC, Wu CH, An J, Wu CC, Liu TZ, et al. Glucose-regulated protein 78 (GRP78) silencing enhances cell migration but does not influence cell proliferation in hepatocellular carcinoma. Ann Surg Oncol. 2010;17:1703–9. Chiou JF, Tai CJ, Huang MT, Wei PL, Wang YH, An J, et al. Glucose-regulated protein 78 is a novel contributor to acquisition of resistance to sorafenib in hepatocellular carcinoma. Ann Surg Oncol. 2010;17:603–12. Cheng AL, Kang YK, Chen Z, Tsao CJ, Qin S, Kim JS, 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. 2009;10:25–34. Wang SK, Liang PH, Astronomo RD, Hsu TL, Hsieh SL, Burton DR, et al. Targeting the carbohydrates on HIV-1: interaction of oligomannose dendrons with human monoclonal antibody 2G12 and DC-SIGN. Proc Natl Acad Sci USA. 2008;105:3690–5. Sowinski S, Jolly C, Berninghausen O, Purbhoo MA, Chauveau A, Köhler K, et al. Membrane nanotubes physically connect T cells over long distances presenting a novel route for HIV-1 transmission. Nat Cell Biol. 2008;10:211–9. Monzo M, Rosell R, Felip E, Astudillo J, Sánchez JJ, Maestre J, et al. A novel anti-apoptosis gene: re-expression of survivin messenger RNA as a prognosis marker in non-small-cell lung cancers. J Clin Oncol. 1999;17:2100–4. Satoh K, Kaneko K, Hirota M, Masamune A, Satoh A, Shimosegawa T. Tumor necrosis factor-related apoptosis-inducing ligand and its receptor expression and the pathway of apoptosis in human pancreatic cancer. Pancreas. 2001;23:251–8. Kawasaki H, Altieri DC, Lu CD, Toyoda M, Tenjo T, Tanigawa N. Inhibition of apoptosis by survivin predicts shorter survival rates in colorectal cancer. Cancer Res. 1998;58:5071–4. Tai CJ, Chin-Sheng H, Kuo LJ, Wei PL, Lu HH, Chen HA, et al. Survivin-mediated cancer cell migration through GRP78 and epithelial-mesenchymal transition (EMT) marker expression in Mahlavu cells. Ann Surg Oncol. 2012;19:336–43. Watson JL, Greenshields A, Hill R, Hilchie A, Lee PW, Giacomantonio CA, et al. Curcumin-induced apoptosis in ovarian carcinoma cells is p53-independent and involves p38 mitogen-activated protein kinase activation and downregulation of Bcl-2 and survivin expression and Akt signaling. Mol Carcinog. 2010;49:13–24. Allegra CJ, Jessup JM, Somerfield MR, Hamilton SR, Hammond EH, Hayes DF, et al. American Society of Clinical Oncology provisional clinical opinion: testing for KRAS gene mutations in patients with metastatic colorectal carcinoma to predict response to anti-epidermal growth factor receptor monoclonal antibody therapy. J Clin Oncol. 2009;27:2091–6. Dean-Colomb W, Esteva FJ. Her2-positive breast cancer: herceptin and beyond. Eur J Cancer. 2008;44:2806–12.