Inhibition of heat shock protein 90 suppresses squamous carcinogenic progression in a mouse model of esophageal cancer

详细信息    查看全文

• 作者：Shaoxiang Wang ; Zhan Du ; Jie Luo ; Xiao Wang…
• 关键词：Hsp90 ; SNX ; 2112 ; ESCC ; 4NQO ; AKT ; Immunocompetent mice model
• 刊名：Journal of Cancer Research and Clinical Oncology
• 出版年：2015
• 出版时间：August 2015
• 年：2015
• 卷：141
• 期：8
• 页码：1405-1416
• 全文大小：8,884 KB
• 参考文献：Akiyama H, Tsurumaru M, Kawamura T, Ono Y (1981) Principles of surgical treatment for carcinoma of the esophagus: analysis of lymph node involvement. Ann Surg 194(4):438-46PubMed Central PubMed View Article
  Bao XH, Takaoka M, Hao HF, Fukazawa T, Yamatsuji T, Sakurama K, Takigawa N, Nakajima M, Fujiwara T, Naomoto Y (2013) Antiproliferative effect of the HSP90 inhibitor NVP-AUY922 is determined by the expression of PTEN in esophageal cancer. Oncol Rep 29(1):45-0. doi:10.-892/?or.-012.-074 PubMed
  Baselga J, Rischin D, Ranson M, Calvert H, Raymond E, Kieback DG, Kaye SB, Gianni L, Harris A, Bjork T, Averbuch SD, Feyereislova A, Swaisland H, Rojo F, Albanell J (2002) Phase I safety, pharmacokinetic, and pharmacodynamic trial of ZD1839, a selective oral epidermal growth factor receptor tyrosine kinase inhibitor, in patients with five selected solid tumor types. J Clin Oncol 20(21):4292-302PubMed View Article
  Biamonte MA, Van de Water R, Arndt JW, Scannevin RH, Perret D, Lee WC (2010) Heat shock protein 90: inhibitors in clinical trials. J Med Chem 53(1):3-7. doi:10.-021/?jm9004708 PubMed View Article
  Chandarlapaty S, Sawai A, Ye Q, Scott A, Silinski M, Huang K, Fadden P, Partdrige J, Hall S, Steed P, Norton L, Rosen N, Solit DB (2008) SNX2112, a synthetic heat shock protein 90 inhibitor, has potent antitumor activity against HER kinase-dependent cancers. Clin Cancer Res 14(1):240-48. doi:10.-158/-078-0432.?CCR-07-1667 PubMed Central PubMed View Article
  Czerninski R, Amornphimoltham P, Patel V, Molinolo AA, Gutkind JS (2009) Targeting mammalian target of rapamycin by rapamycin prevents tumor progression in an oral-specific chemical carcinogenesis model. Cancer Prev Res (Phila) 2(1):27-6. doi:10.-158/-940-6207.?CAPR-08-0147 View Article
  Ekman S, Bergqvist M, Tell R, Bergstrom S, Lennartsson J (2010) Hsp90 as a therapeutic target in patients with oesophageal carcinoma. Expert Opin Ther Targets 14(3):317-28. doi:10.-517/-472822100362127- PubMed View Article
  Faried A, Sohda M, Nakajima M, Miyazaki T, Kato H, Kuwano H (2004) Expression of heat-shock protein Hsp60 correlated with the apoptotic index and patient prognosis in human oesophageal squamous cell carcinoma. Eur J Cancer 40(18):2804-811. doi:10.-016/?j.?ejca.-004.-8.-13 PubMed View Article
  Fong LY, Lau KM, Huebner K, Magee PN (1997) Induction of esophageal tumors in zinc-deficient rats by single low doses of N-nitrosomethylbenzylamine (NMBA): analysis of cell proliferation, and mutations in H-ras and p53 genes. Carcinogenesis 18(8):1477-484PubMed View Article
  Hong DS, Banerji U, Tavana B, George GC, Aaron J, Kurzrock R (2013) Targeting the molecular chaperone heat shock protein 90 (HSP90): lessons learned and future directions. Cancer Treat Rev 39(4):375-87. doi:10.-016/?j.?ctrv.-012.-0.-01 PubMed View Article
  Huang KH, Veal JM, Fadden RP, Rice JW, Eaves J, Strachan JP, Barabasz AF, Foley BE, Barta TE, Ma W, Silinski MA, Hu M, Partridge JM, Scott A, DuBois LG, Freed T, Steed PM, Ommen AJ, Smith ED, Hughes PF, Woodward AR, Hanson GJ, McCall WS, Markworth CJ, Hinkley L, Jenks M, Geng L, Lewis M, Otto J, Pronk B, Verleysen K, Hall SE (2009) Discovery of novel 2-aminobenzamide inhibitors of heat shock protein 90 as potent, selective and orally active antitumor agents. J Med Chem 52(14):4288-305. doi:10.-021/?jm900230j PubMed View Article
  Jemal A, Bray F, Center MM, Ferlay J, Ward E, Forman D (2011) Global cancer statistics. CA Cancer J Clin 61(2):69-0. doi:10.-322/?caac.-0107 PubMed View Article
  Jin L, Xiao CL, Lu CH, Xia M, Xing GW, Xiong S, Liu QY, Liu H, Li YC, Ge F, Wang QD, He QY, Wang YF (2009) Transcriptomic and proteomic approach to studying SNX-2112-induced K562 cells apoptosis and anti-leukemia activity in K562-NOD/SCID mice. FEBS Lett 583(12):1859-866. doi:10.-016/?j.?febslet.-009.-4.-46 PubMed View Article
  Ju HQ, Wang SX, Xiang YF, Liu Z, Liu JY, Chen ZP, Zeng FL, Xia M, Liu ZH, Xing GW, Wang SY, Wang YF (2011a) BJ-B11, a novel Hsp90 inhibitor, induces apoptosis in human chronic myeloid leukemia K562 cells through the mitochondria-dependent pathway. Eur J Pharmacol 666(1-):26-4. doi:10.-016/?j.?ejphar.-011.-5.-20 PubMed View Article
  Ju HQ, Xiang YF, Xin BJ, Pei Y, Lu JX, Wang QL, Xia M, Qian CW, Ren Z, Wang SY, Wang YF, Xing GW (2011b) Synthesis and in vitro anti-HSV-1 activity of a novel Hsp90 inhibitor BJ-B11. Bioorg Med Chem Lett 21(6):1675-677. doi:10.-016/?j.?bmcl.-011.-1.-98 PubMed View Article
  King MA, Scotty N, Klein RL, Meyer EM (2002) Particle detection, number estimation, and feature measurement in gene transfer studies: optical fractionator stereology integrated with digital image processing and analysis. Methods 28(2):293-99PubMed View Article
  Lam AK (2000) Molecular biology of esophageal squamous cell carcinoma. Crit Rev Oncol Hematol 33(2):71-0PubMed View Article
  Li H, Gao Q, Guo L, Lu SH (2011) The PTEN/PI3K/Akt pathway
• 作者单位：Shaoxiang Wang (3)
  Zhan Du (4)
  Jie Luo (4)
  Xiao Wang (2)
  Haiying Li (1)
  Yuting Liu (2)
  Yong Zhang (1)
  Jiwei Ma (1)
  Weiwei Xiao (5)
  Yifei Wang (2)
  Xueyun Zhong (1)
  
  3. Institute of Molecular Medicine, Department of Medicine, Shenzhen University, Shenzhen, People’s Republic of China
  4. The Second Affiliated Hospital of Nanchang University, Nanchang, 330006, Jiangxi Province, People’s Republic of China
  2. Guangzhou Jinan Biomedicine Research and Development Center, National Engineering Research Center of Genetic Medicine, Jinan University, Guangzhou, 510632, Guangdong Province, People’s Republic of China
  1. Department of Pathology, Medical College, Guangdong Province Key Laboratory of Molecule Immunology and Antibody Engineering, Jinan University, Guangzhou, 510632, People’s Republic of China
  5. Department of Radiation Oncology, Cancer Centre, Sun Yat-sen University, Guangzhou, 510120, Guangdong Province, People’s Republic of China
  
• 刊物类别：Medicine
• 刊物主题：Medicine & Public Health
  Oncology
  Cancer Research
  Internal Medicine
  Hematology
  
• 出版者：Springer Berlin / Heidelberg
• ISSN：1432-1335

文摘

Purpose Heat shock protein 90 (Hsp90), a potential therapeutic target, has been widely recognized in vitro and in vivo in immunodeficient mice. Here, we aimed to evaluate the role of Hsp90 in an immunocompetent mouse model of esophageal squamous cell cancer (ESCC). Methods The carcinogen 4-nitroquinoline 1-oxide (4NQO) was used to induce ESCC in C57BL/6 mice. Cancer progression was analyzed through observation of appearance, hematoxylin–eosin staining, immunohistochemical detection, and terminal dUTP nick-end labeling analysis. Results 4NQO led to the progressive appearance of preneoplastic and tumoral lesions in the esophagus, with 100?% incidence of ESCC in situ occurring only after 16?weeks of carcinogen exposure. Most of these lesions evolved spontaneously into highly invasive ESCC even after 4NQO withdrawal (weeks 16-2). Interestingly, there was marked upregulation of Hsp90 and its client proteins in tumoral lesions at 22?weeks. Hsp90 inhibition by intraperitoneal injection of SNX-2112 over the following 2?weeks downregulated AKT and cyclin D1 expression, leading to significant reduction in tumor incidence and prevention of ESCC progression. Moreover, SNX-2112 treatment decreased proliferating cell nuclear antigen expression and increased the number of apoptotic cells in ESCC tissues. Conclusions Our in vivo findings support the contribution of Hsp90 to ESCC progression, which was achieved by stimulating apoptosis and inhibition of cell proliferation, and provide a strong rationale for further evaluation of Hsp90 inhibitors for treating ESCC.