Chemotherapy and radiotherapy are two indispensible methods for esophageal squamous cell carcinoma (ESCC), especially for those recurring and metastatic ones, but therapeutic toxicity remains a major problem to overcome. In the present study, the potential therapeutic value of nimotuzumab (an antiepidermal growth factor receptor [EGFR] monoclonal antibody) in combination with chemotherapy and radiotherapy was evaluated on Eca109 and TE-1 ESCC cells, with high and low expression of EGFR, respectively. It was shown that nimotuzumab enhanced the sensitivity of Eca109 cells to other cytotoxic agents (paclitaxel and cis-platinum) and X-ray radiation, and the cytotoxicity was associated with increased autophagy. Conversely, the chemo- and radio-sensitivity of TE-1 cells showed no improvement with addition of nimotuzumab, but could be increased by combining with rapamycin, an autophagy inducer. Therefore, it was concluded that autophagic activation mediated by nimotuzumab could promote autophagic cell death and produce additive antitumor effects.
JemalA. Global cancer statistics. CA Cancer J Clin2011; 61: 134–134.
2.
ParkBBImYHHwangIGLeeSCAhnJSAhnMJLimHYKangWKParkK. Salvage chemotherapy with mitomycin C, ifosfamide, and cisplatin (MIC) for previously treated metastatic or recurrent esophageal squamous cell carcinoma. Invest New Drugs2008; 26: 387–92.
3.
JinJXuXWangFYanGLiuJLuWLiXTuckerSJZhongBCaoZWangD. Second-line combination chemotherapy with docetaxel and nedaplatin for Cisplatin-pretreated refractory metastatic/recurrent esophageal squamous cell carcinoma. J Thorac Oncol2009; 4: 1017–21.
4.
TepperJKrasnaMJNiedzwieckiDHollisDReedCEGoldbergRKielKWillettCSugarbakerDMayerR. Phase III trial of trimodality therapy with cisplatin, fluorouracil, radiotherapy, and surgery compared with surgery alone for esophageal cancer: CALGB 9781. J Clin Oncol2008; 26: 1086–92.
5.
GibaultLMetgesJPConan-CharletVLozac'hPRobaszkiewiczMBessaguetCLagardeNVolantA. Diffuse EGFR staining is associated with reduced overall survival in locally advanced oesophageal squamous cell cancer. Br J Cancer2005; 93: 107–15.
6.
WilkinsonNWBlackJDRoukhadzeEDriscollDSmileySHoshiHGeradtsJJavleMBrattainM. Epidermal growth factor receptor expression correlates with histologic grade in resected esophageal adenocarcinoma. J Gastrointest Surg2004; 8: 448–53.
7.
RosellRVergnenegreALiuBCoboMMassutiBWeiJMolinaMACostaCQueraltCTaronM. Biomarkers in lung oncology. Pulm Pharmacol Ther2010; 23: 508–14.
8.
ChakravartiAWinterKWuCLKaufmanDHammondEParliamentMTesterWHaganMGrignonDHeneyNPollackASandlerHShipleyW. Expression of the epidermal growth factor receptor and Her-2 are predictors of favorable outcome and reduced complete response rates, respectively, in patients with muscle-invading bladder cancers treated by concurrent radiation and cisplatin-based chemotherapy: A report from the Radiation Therapy Oncology Group. Int J Radiat Oncol Biol Phys2005; 62: 309–17.
9.
VordermarkDKolblO. Lack of survival benefit after stereotactic radiosurgery boost for glioblastoma multiforme: Randomized comparison of stereotactic radiosurgery followed by conventional radiotherapy with carmustine to conventional radiotherapy with carmustine for patients with glioblastoma multiforme: Report of radiation therapy oncology group 93-05 protocol: In regard to Souhami et al. Int J Radiat Oncol Biol Phys2005; 62: 296–7.
10.
YangZKlionskyDJ. Eaten alive: A history of macroautophagy. Nat Cell Biol2010; 12: 814–22.
11.
LevineBKroemerG. Autophagy in aging, disease and death: the true identity of a cell death impostor. Cell Death Differ2009; 16: 1–2.
12.
TalaveraAFriemannRGomez-PuertaSMartinez-FleitesCGarridoGRabasaALopez-RequenaAPupoAJohansenRFSanchezOKrengelUMorenoE. Nimotuzumab, an antitumor antibody that targets the epidermal growth factor receptor, blocks ligand binding while permitting the active receptor conformation. Cancer Res2009; 69: 5851–9.
13.
CrombetTOsorioMCruzTRocaCdel CastilloRMonRIznaga-EscobarNFigueredoRKoropatnickJRenginfoEFernandezEAlvarezDTorresOLeonardIPerezRLageA. Use of the humanized anti-epidermal growth factor receptor monoclonal antibody h-R3 in combination with radiotherapy in the treatment of locally advanced head and neck cancer patients. J Clin Oncol2004; 22: 1646–54.
14.
RamosTCFigueredoJCatalaMGonzalezSSelvaJCCruzTMToledoCSilvaSPestanoYRamosMLeonardITorresOMarinelloPPerezRLageA. Treatment of high-grade glioma patients with the humanized anti-epidermal growth factor receptor (EGFR) antibody h-R3: Report from a phase I/II trial. Cancer Biol Ther2006; 5: 375–9.
15.
HuangYYuTFuXChenJLiuYLiCXiaYZhangZLiL. EGFR inhibition prevents in vitro tumor growth of salivary adenoid cystic carcinoma. BMC Cell Biol2013; 14: 13–13.
16.
ZhaoLLiQQZhangRXiMLiaoYJQianDHeLRZengYXXieDLiuMZ. The overexpression of IGFBP-3 is involved in the chemosensitivity of esophageal squamous cell carcinoma cells to nimotuzumab combined with cisplatin. Tumour Biol2012; 33: 1115–23.
17.
SleeEAZhuHChowSCMacFarlaneMNicholsonDWCohenGM. Benzyloxycarbonyl-Val-Ala-Asp (OMe) fluoromethylketone (Z-VAD.FMK) inhibits apoptosis by blocking the processing of CPP32. Biochem J1996; 315: 21–4.
18.
JinSWhiteE. Role of autophagy in cancer: management of metabolic stress. Autophagy2007; 3: 28–31.
19.
DasAKChenBPStoryMDSatoMMinnaJDChenDJNirodiCS. Somatic mutations in the tyrosine kinase domain of epidermal growth factor receptor (EGFR) abrogate EGFR-mediated radioprotection in non-small cell lung carcinoma. Cancer Res2007; 67: 5267–74.
20.
FungCChenXGrandisJRDuvvuriU. EGFR tyrosine kinase inhibition induces autophagy in cancer cells. Cancer Biol Ther2012; 13: 1417–24.
21.
LiXLuYPanTFanZ. Roles of autophagy in cetuximab-mediated cancer therapy against EGFR. Autophagy2010; 6: 1066–77.
22.
Diaz MiqueliARolffJLemmMFichtnerIPerezRMonteroE. Radiosensitisation of U87MG brain tumours by anti-epidermal growth factor receptor monoclonal antibodies. Br J Cancer2009; 100: 950–8.
23.
AkashiYOkamotoIIwasaTYoshidaTSuzukiMHatashitaEYamadaYSatohTFukuokaMOnoKNakagawaK. Enhancement of the antitumor activity of ionising radiation by nimotuzumab, a humanised monoclonal antibody to the epidermal growth factor receptor, in non-small cell lung cancer cell lines of differing epidermal growth factor receptor status. Br J Cancer2008; 98: 749–55.
24.
GarridoGTikhomirovIARabasaAYangEGraciaEIznagaNFernandezLECrombetTKerbelRSPerezR. Bivalent binding by intermediate affinity of nimotuzumab: A contribution to explain antibody clinical profile. Cancer Biol Ther2011; 11: 373–82.
25.
ChuQAmanoOKandaYKuniiSWangQSakagamiH. Tumor-specific cytotoxicity and type of cell death induced by gefitinib in oral squamous cell carcinoma cell lines. Anticancer Res2009; 29: 5023–31.
26.
LiXLuworRLuYLiangKFanZ. Enhancement of antitumor activity of the anti-EGF receptor monoclonal antibody cetuximab/C225 by perifosine in PTEN-deficient cancer cells. Oncogene2006; 25: 525–35.
27.
LuYLiXLiangKLuworRSiddikZHMillsGBMendelsohnJFanZ. Epidermal growth factor receptor (EGFR) ubiquitination as a mechanism of acquired resistance escaping treatment by the anti-EGFR monoclonal antibody cetuximab. Cancer Res2007; 67: 8240–7.
28.
LiXFanZ. The epidermal growth factor receptor antibody cetuximab induces autophagy in cancer cells by downregulating HIF-1alpha and Bcl-2 and activating the beclin 1/hVps34 complex. Cancer Res2010; 70: 5942–52.
