Login Register Cart 0
General Research Article

利用腺病毒载体携带REIC/Dkk-3基因治疗胆道癌的前景

卷 20, 期 1, 2020

页: [64 - 70] 页: 7

弟呕挨: 10.2174/1566523220666200309125709

价格: $65

conference banner
摘要

背景:我们之前证实，在各种恶性肿瘤中，永久细胞(REIC)/dikkopf-3 (Dkk-3)基因表达降低，而携带REIC/Dkk-3基因的腺病毒载体被称为Ad-REIC诱导的胰腺癌和肝癌的选择性凋亡。 目的:本研究采用第二代Ad-REIC (Ad-SGE-REIC)检测Ad-REIC对胆道癌的治疗效果。 方法:采用人胆道癌细胞系(G-415, TFK-1)进行研究。体外采用MTT法和Hoechst染色检测Ad-SGE-REIC的细胞存活率和凋亡效应。在小鼠异种移植模型中评估其体内抗肿瘤作用。我们也评估了顺铂对Ad-SGE-REIC治疗的疗效。Western blotting检测细胞信号转导。 结果:Ad-SGE-REIC通过激活c-Jun n末端激酶途径，降低了胆道癌细胞的细胞活力，诱导细胞凋亡。在小鼠异种移植模型中，Ad-SGE-REIC也能抑制肿瘤生长。与顺铂联合用药后，这一效果进一步增强。 结论:Ad-SGE-REIC可诱导胆道癌细胞凋亡，抑制肿瘤生长。REIC/Dkk-3基因治疗Ad-SGE-REIC是一种很有吸引力的胆道癌治疗工具。

关键词: REIC/Dkk-3

« Previous Next »
图形摘要

[1]
Siegel RL, Miller KD, Jemal A. Cancer statistics, 2019. CA Cancer J Clin 2019; 69(1): 7-34.
[http://dx.doi.org/10.3322/caac.21551] [PMID: 30620402]
[2]
Doherty B, Nambudiri VE, Palmer WC. Update on the diagnosis and treatment of cholangiocarcinoma. Curr Gastroenterol Rep 2017; 19(1): 2.
[http://dx.doi.org/10.1007/s11894-017-0542-4] [PMID: 28110453]
[3]
Valle J, Wasan H, Palmer DH, et al. Cisplatin plus gemcitabine versus gemcitabine for biliary tract cancer. N Engl J Med 2010; 362(14): 1273-81.
[http://dx.doi.org/10.1056/NEJMoa0908721] [PMID: 20375404]
[4]
Okusaka T, Nakachi K, Fukutomi A, et al. Gemcitabine alone or in combination with cisplatin in patients with biliary tract cancer: a comparative multicentre study in Japan. Br J Cancer 2010; 103(4): 469-74.
[http://dx.doi.org/10.1038/sj.bjc.6605779] [PMID: 20628385]
[5]
Tsuji T, Miyazaki M, Sakaguchi M, Inoue Y, Namba M. A REIC gene shows down-regulation in human immortalized cells and human tumor-derived cell lines. Biochem Biophys Res Commun 2000; 268(1): 20-4.
[http://dx.doi.org/10.1006/bbrc.1999.2067] [PMID: 10652205]
[6]
Abarzua F, Sakaguchi M, Takaishi M, et al. Adenovirus-mediated overexpression of REIC/Dkk-3 selectively induces apoptosis in human prostate cancer cells through activation of c-Jun-NH2-kinase. Cancer Res 2005; 65(21): 9617-22.
[http://dx.doi.org/10.1158/0008-5472.CAN-05-0829] [PMID: 16266978]
[7]
Uchida D, Shiraha H, Kato H, et al. Potential of adenovirus-mediated REIC/Dkk-3 gene therapy for use in the treatment of pancreatic cancer. J Gastroenterol Hepatol 2014; 29(5): 973-83.
[http://dx.doi.org/10.1111/jgh.12501] [PMID: 24372695]
[8]
Edamura K, Nasu Y, Takaishi M, et al. Adenovirus-mediated REIC/Dkk-3 gene transfer inhibits tumor growth and metastasis in an orthotopic prostate cancer model. Cancer Gene Ther 2007; 14(9): 765-72.
[http://dx.doi.org/10.1038/sj.cgt.7701071] [PMID: 17599093]
[9]
Kawasaki K, Watanabe M, Sakaguchi M, et al. REIC/Dkk-3 overexpression downregulates P-glycoprotein in multidrug-resistant MCF7/ADR cells and induces apoptosis in breast cancer. Cancer Gene Ther 2009; 16(1): 65-72.
[http://dx.doi.org/10.1038/cgt.2008.58] [PMID: 18654608]
[10]
Gonzalez-Carmona MA, Bolch M, Jansen C, et al. Combined photodynamic therapy with systemic chemotherapy for unresectable cholangiocarcinoma. Aliment Pharmacol Ther 2019; 49(4): 437-47.
[http://dx.doi.org/10.1111/apt.15050] [PMID: 30637783]
[11]
André T, Tournigand C, Rosmorduc O, et al. Gemcitabine combined with oxaliplatin (GEMOX) in advanced biliary tract adenocarcinoma: a GERCOR study. Ann Oncol 2004; 15(9): 1339-43.
[http://dx.doi.org/10.1093/annonc/mdh351] [PMID: 15319238]
[12]
Morizane C, Okusaka T, Mizusawa J, et al. Randomized phase III study of gemcitabine plus S-1 combination therapy versus gemcitabine plus cisplatin combination therapy in advanced biliary tract cancer: A Japan Clinical Oncology Group study (JCOG1113, FUGA- BT). J Clin Oncol 2016; 46(4_suppl): 205-5.
[http://dx.doi.org/10.1093/jjco/hyv213] [PMID: 27025903]
[13]
Sakai D, Kanai M, Kobayashi S, et al. Randomized phase III study of gemcitabine, cisplatin plus S-1 (GCS) versus gemcitabine, cisplatin (GC) for advanced biliary tract cancer (KHBO1401- MITSUBA). Ann Oncol 2018; 29(suppl_8): viii205-70.
[http://dx.doi.org/10.1093/annonc/mdy282]
[14]
Conroy T, Desseigne F, Ychou M, et al. FOLFIRINOX versus gemcitabine for metastatic pancreatic cancer. N Engl J Med 2011; 364(19): 1817-25.
[http://dx.doi.org/10.1056/NEJMoa1011923] [PMID: 21561347]
[15]
Von Hoff DD, Ervin T, Arena FP, et al. Increased survival in pancreatic cancer with nab-paclitaxel plus gemcitabine. N Engl J Med 2013; 369(18): 1691-703.
[http://dx.doi.org/10.1056/NEJMoa1304369] [PMID: 24131140]
[16]
Golan T, Hammel P, Reni M, et al. Maintenance olaparib for germline BRCA-Mutated metastatic pancreatic cancer. N Engl J Med 2019; 381(4): 317-27.
[http://dx.doi.org/10.1056/NEJMoa1903387] [PMID: 31157963]
[17]
Rizvi S, Khan SA, Hallemeier CL, Kelley RK, Gores GJ. Cholangiocarcinoma - evolving concepts and therapeutic strategies. Nat Rev Clin Oncol 2018; 15(2): 95-111.
[http://dx.doi.org/10.1038/nrclinonc.2017.157] [PMID: 28994423]
[18]
Tella SH, Kommalapati A, Borad MJ, Mahipal A. Second-line therapies in advanced biliary tract cancers. Lancet Oncol 2020; 21(1): e29-41.
[http://dx.doi.org/10.1016/S1470-2045(19)30733-8] [PMID: 31908303]
[19]
Javle M, Churi C, Kang HC, et al. HER2/neu-directed therapy for biliary tract cancer. J Hematol Oncol 2015; 8(1): 58.
[http://dx.doi.org/10.1186/s13045-015-0155-z] [PMID: 26022204]
[20]
Javle M, Zhao H, Abou-Alfa GK. Systemic therapy for gallbladder cancer. Linchuang Zhongliuxue Zazhi 2019; 8(4): 44.
[http://dx.doi.org/10.21037/cco.2019.08.14] [PMID: 31484490]
[21]
Javle M, Lowery M, Shroff RT, et al. Phase II study of BGJ398 in patients with FGFR-Altered advanced cholangiocarcinoma. J Clin Oncol 2018; 36(3): 276-82.
[http://dx.doi.org/10.1200/JCO.2017.75.5009] [PMID: 29182496]
[22]
Yang P, Javle M, Pang F, et al. Somatic genetic aberrations in gallbladder cancer: comparison between Chinese and US patients. Hepatobiliary Surg Nutr 2019; 8(6): 604-14.
[http://dx.doi.org/10.21037/hbsn.2019.04.11] [PMID: 31929987]
[23]
Kashiwakura Y, Ochiai K, Watanabe M, et al. Down-regulation of inhibition of differentiation-1 via activation of activating transcription factor 3 and Smad regulates REIC/Dickkopf-3-induced apoptosis. Cancer Res 2008; 68(20): 8333-41.
[http://dx.doi.org/10.1158/0008-5472.CAN-08-0080] [PMID: 18922905]
[24]
Sawahara H, Shiraha H, Uchida D, et al. Promising therapeutic efficacy of a novel reduced expression in immortalized cells/dickkopf-3 expressing adenoviral vector for hepatocellular carcinoma. J Gastroenterol Hepatol 2017; 32(10): 1769-77.
[http://dx.doi.org/10.1111/jgh.13757] [PMID: 28168749]
[25]
Shien K, Tanaka N, Watanabe M, et al. Anti-cancer effects of REIC/Dkk-3-encoding adenoviral vector for the treatment of non-small cell lung cancer. PLoS One 2014; 9(2)e87900
[http://dx.doi.org/10.1371/journal.pone.0087900] [PMID: 24498395]
[26]
Watanabe M, Nasu Y, Kumon H. Adenovirus-mediated REIC/Dkk-3 gene therapy: Development of an autologous cancer vaccination therapy (Review). Oncol Lett 2014; 7(3): 595-601.
[http://dx.doi.org/10.3892/ol.2013.1777] [PMID: 24527065]
[27]
Mizuguchi H, Koizumi N, Hosono T, et al. A simplified system for constructing recombinant adenoviral vectors containing heterologous peptides in the HI loop of their fiber knob. Gene Ther 2001; 8(9): 730-5.
[http://dx.doi.org/10.1038/sj.gt.3301453] [PMID: 11406768]
[28]
Croyle MA, Yu QC, Wilson JM. Development of a rapid method for the PEGylation of adenoviruses with enhanced transduction and improved stability under harsh storage conditions. Hum Gene Ther 2000; 11(12): 1713-22.
[http://dx.doi.org/10.1089/10430340050111368] [PMID: 10954905]
[29]
Sawahara H, Shiraha H, Uchida D, et al. Novel REIC/Dkk-3-encoding adenoviral vector as a promising therapeutic agent for pancreatic cancer. Cancer Gene Ther 2016; 23(8): 278-83.
[30]
Watanabe M, Kashiwakura Y, Huang P, et al. Immunological aspects of REIC/Dkk-3 in monocyte differentiation and tumor regression. Int J Oncol 2009; 34(3): 657-63.
[http://dx.doi.org/10.3892/ijo_00000191] [PMID: 19212670]
[31]
Uchida D, Shiraha H, Kato H, et al. Synergistic anti-pancreatic cancer immunological effects by treatment with reduced expression in immortalized cells/dickkopf-3 protein and peripheral blood mononuclear cells. J Gastroenterol Hepatol 2016; 31(6): 1154-9.
[http://dx.doi.org/10.1111/jgh.13259] [PMID: 26643412]
[32]
Le DT, Uram JN, Wang H, et al. PD-1 blockade in tumors with mismatch-repair deficiency. N Engl J Med 2015; 372(26): 2509-20.
[http://dx.doi.org/10.1056/NEJMoa1500596] [PMID: 26028255]
[33]
Feng M, Xiong G, Cao Z, et al. PD-1/PD-L1 and immunotherapy for pancreatic cancer. Cancer Lett 2017; 407: 57-65.
[http://dx.doi.org/10.1016/j.canlet.2017.08.006] [PMID: 28826722]
[34]
Liu X, Yao J, Song L, Zhang S, Huang T, Li Y. Local and abscopal responses in advanced intrahepatic cholangiocarcinoma with low TMB, MSS, pMMR and negative PD-L1 expression following combined therapy of SBRT with PD-1 blockade. J Immunother Cancer 2019; 7(1): 204.
[http://dx.doi.org/10.1186/s40425-019-0692-z] [PMID: 31383016]

Rights & Permissions Print Cite
Article Metrics
17
1
Wayfinder Image
© 2024 Bentham Science Publishers | Privacy Policy