Proteasome inhibitor MG132 inhibits the proliferation and promotes the cisplatin-induced apoptosis of human esophageal squamous cell carcinoma cells

Dang,Lifeng; Wen,Fengbiao; Yang,Yang; Liu,Donglei; Wu,Kai; Qi,Yu; Li,Xiangnan; Zhao,Jia; Zhu,Dengyan; Zhang,Chunyang; Zhao,Song

doi:10.3892/ijmm.2014.1678

Proteasome inhibitor MG132 inhibits the proliferation and promotes the cisplatin-induced apoptosis of human esophageal squamous cell carcinoma cells

Authors:
- Lifeng Dang
- Fengbiao Wen
- Yang Yang
- Donglei Liu
- Kai Wu
- Yu Qi
- Xiangnan Li
- Jia Zhao
- Dengyan Zhu
- Chunyang Zhang
- Song Zhao
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Affiliations: Physical Examination Centre, First Affiliated Hospital, Zhengzhou University, Zhengzhou, Henan 450052, P.R. China, Department of Thoracic Surgery, First Affiliated Hospital, Zhengzhou University, Zhengzhou, Henan 450052, P.R. China
Published online on: February 27, 2014 https://doi.org/10.3892/ijmm.2014.1678
Pages: 1083-1088
Copyright: © Dang et al. This is an open access article distributed under the terms of Creative Commons Attribution License [CC BY_NC 3.0].

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Abstract

Comprehensive treatment based on chemotherapy is regarded as the first-line treatment for patients with unresectable or metastatic esophageal squamous cell carcinoma (ESCC). However, chemoresistance is common among patients with ESCC. Therefore, there is a need to explore new therapeutic strategies or adjuvant drugs. One promising possibility is to use dietary agents that can increase tumor cell sensitivity to drugs. In this study, we initially investigated the antitumor activity of proteasome inhibitor MG132 in vitro and in vivo. Effects of MG132 on the enhancment of the anticancer functions of cisplatin were then investigated in human esophageal cancer EC9706 cells in relation to apoptosis and cell signaling events. Exposure of cells to MG132 resulted in a marked decrease in cell viability in a dose- and time-dependent manner. Administration of MG132 markedly inhibited tumor growth in the EC9706 xenograft model. MG132 significantly enhanced cisplatin-induced apoptosis in association with the activation of caspase-3 and -8. These events were accompanied by the downregulation of NF-κB, which plays a key role in cell apoptosis. Taken together, these findings demonstrate a novel mechanism by which proteasome inhibitor MG132 potentiates cisplatin-induced apoptosis in human ESCC and inhibitory activity of tumor growth of the EC9706 xenograft model.

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1	van Hagen P, Hulshof MC, van Lanschot JJ, et al: Preoperative chemoradiotherapy for esophageal or junctional cancer. N Engl J Med. 366:2074–2084. 2012.
2	Tomblyn MB, Goldman BH, Thomas CR Jr, et al: Cetuximab plus cisplatin, irinotecan, and thoracic radiotherapy as definitive treatment for locally advanced, unresectable esophageal cancer: a phase-II study of the SWOG (S0414). J Thorac Oncol. 7:906–912. 2012. View Article : Google Scholar
3	Murtaza M, Dawson SJ, Tsui DW, et al: Non-invasive analysis of acquired resistance to cancer therapy by sequencing of plasma DNA. Nature. 497:108–112. 2013. View Article : Google Scholar : PubMed/NCBI
4	Gao D, Hu J, Zhang X, Gao C and Hong J: Effect of hOGG1 over-expression on cisplatin resistance in esophageal squamous carcinoma cells. Cancer Biother Radiopharm. 28:433–440. 2013. View Article : Google Scholar : PubMed/NCBI
5	Khedgikar V, Kushwaha P, Gautam J, et al: Withaferin A: a proteasomal inhibitor promotes healing after injury and exerts anabolic effect on osteoporotic bone. Cell Death Dis. 4:e7782013. View Article : Google Scholar : PubMed/NCBI
6	Li X, Huang T, Jiang G, Gong W, Qian H and Zou C: Proteasome inhibitor MG132 enhances TRAIL-induced apoptosis and inhibits invasion of human osteosarcoma OS732 cells. Biochem Biophys Res Commun. 439:179–186. 2013. View Article : Google Scholar : PubMed/NCBI
7	Stoll SJ, Pitt SC and Chen H: Follicular thyroid cancer cell growth inhibition by proteosome inhibitor MG132. J Surg Res. 156:39–44. 2009. View Article : Google Scholar : PubMed/NCBI
8	Duraj J, Pastorek M, Vitkovska J, et al: Proteasome inhibition leads to altered signaling in the proteome of cisplatin-resistant human ovarian carcinoma cell line. Neoplasma. 60:627–634. 2013. View Article : Google Scholar : PubMed/NCBI
9	Fribley AM, Evenchik B, Zeng Q, et al: Proteasome inhibitor PS-341 induces apoptosis in cisplatin-resistant squamous cell carcinoma cells by induction of Noxa. J Biol Chem. 281:31440–31447. 2006. View Article : Google Scholar : PubMed/NCBI
10	Fribley A, Zeng Q and Wang CY: Proteasome inhibitor PS-341 induces apoptosis through induction of endoplasmic reticulum stress-reactive oxygen species in head and neck squamous cell carcinoma cells. Mol Cell Biol. 24:9695–9704. 2004. View Article : Google Scholar
11	He YF, Ji CS, Hu B, et al: A phase II study of paclitaxel and nedaplatin as front-line chemotherapy in Chinese patients with metastatic esophageal squamous cell carcinoma. World J Gastroenterol. 19:5910–5916. 2013. View Article : Google Scholar : PubMed/NCBI
12	Kurosu T, Nagao T, Wu N, Oshikawa G and Miura O: Inhibition of the PI3K/Akt/GSK3 pathway downstream of BCR/ABL, Jak2-V617F, or FLT3-ITD downregulates DNA damage-induced Chk1 activation as well as G2/M arrest and prominently enhances induction of apoptosis. PLoS One. 8:e794782013. View Article : Google Scholar : PubMed/NCBI
13	Chen WW, Lin CC, Huang TC, Cheng AL, Yeh KH and Hsu CH: Prognostic factors of metastatic or recurrent esophageal squamous cell carcinoma in patients receiving three-drug combination chemotherapy. Anticancer Res. 33:4123–4128. 2013.PubMed/NCBI
14	Shi Y, Qin R, Wang ZK and Dai GH: Nanoparticle albumin-bound paclitaxel combined with cisplatin as the first-line treatment for metastatic esophageal squamous cell carcinoma. Onco Targets Ther. 6:585–591. 2013. View Article : Google Scholar : PubMed/NCBI
15	Tu Y, Chen C, Pan J, Xu J, Zhou ZG and Wang CY: The Ubiquitin Proteasome Pathway (UPP) in the regulation of cell cycle control and DNA damage repair and its implication in tumorigenesis. Int J Clin Exp Pathol. 5:726–738. 2012.PubMed/NCBI
16	Yang H, Landis-Piwowar K, Chan TH and Dou QP: Green tea polyphenols as proteasome inhibitors: implication in chemoprevention. Curr Cancer Drug Targets. 11:296–306. 2011. View Article : Google Scholar : PubMed/NCBI
17	Kandilis AN, Karidis NP, Kouraklis G, Patsouris E, Vasileiou I and Theocharis S: Proteasome inhibitors: possible novel therapeutic strategy for ischemia-reperfusion injury? Expert Opin Investig Drugs. 23:67–80. 2014. View Article : Google Scholar : PubMed/NCBI
18	Flemming A: Therapeutics: opening the door to a new class of proteasome inhibitors. Nat Rev Cancer. 12:52011. View Article : Google Scholar : PubMed/NCBI
19	Chen FZ and Zhao XK: Ubiquitin-proteasome pathway and prostate cancer. Onkologie. 36:592–596. 2013. View Article : Google Scholar : PubMed/NCBI
20	Gu JJ, Hernandez-Ilizaliturri FJ, Kaufman GP, et al: The novel proteasome inhibitor carfilzomib induces cell cycle arrest, apoptosis and potentiates the anti-tumour activity of chemotherapy in rituximab-resistant lymphoma. Br J Haematol. 162:657–669. 2013. View Article : Google Scholar : PubMed/NCBI
21	Hui B, Shi YH, Ding ZB, et al: Proteasome inhibitor interacts synergistically with autophagy inhibitor to suppress proliferation and induce apoptosis in hepatocellular carcinoma. Cancer. 118:5560–5571. 2012. View Article : Google Scholar : PubMed/NCBI
22	Altmann A, Markert A, Askoxylakis V, et al: Antitumor effects of proteasome inhibition in anaplastic thyroid carcinoma. J Nucl Med. 53:1764–1771. 2012. View Article : Google Scholar : PubMed/NCBI
23	Rastogi N and Mishra DP: Therapeutic targeting of cancer cell cycle using proteasome inhibitors. Cell Div. 7:262012. View Article : Google Scholar : PubMed/NCBI
24	da Cunha FM, Demasi M and Kowaltowski AJ: Aging and calorie restriction modulate yeast redox state, oxidized protein removal, and the ubiquitin-proteasome system. Free Radic Biol Med. 51:664–670. 2011.PubMed/NCBI
25	Chitra S, Nalini G and Rajasekhar G: The ubiquitin proteasome system and efficacy of proteasome inhibitors in diseases. Int J Rheum Dis. 15:249–260. 2012. View Article : Google Scholar : PubMed/NCBI
26	de Almagro MC and Vucic D: The inhibitor of apoptosis (IAP) proteins are critical regulators of signaling pathways and targets for anti-cancer therapy. Exp Oncol. 34:200–211. 2012.PubMed/NCBI
27	Napetschnig J and Wu H: Molecular basis of NF-κB signaling. Annu Rev Biophys. 42:443–468. 2013.