Document Detail

Nimotuzumab increases chemosensitivity of human lung adenocarcinoma cell lines to docetaxel.
MedLine Citation:
PMID:  23035364     Owner:  NLM     Status:  MEDLINE    
Overexpression of epidermal growth factor receptor (EGFR) is common in non-small-cell lung cancer (NSCLC) and has been recently shown to contribute to cancer chemoresistance. It has been reported that the EGFR antibodies such as cetuximab in combination with chemotherapy could lead to an absolute benefit of overall survival (OS) compared with chemotherapy alone. In this study, we investigated the effects of nimotuzumab (h-R3), a humanized anti-EGFR antibody, in combination with docetaxel (DTX), on DTX-resistant human lung adenocarcinoma cell line SPC-A1 (SPC-A1/DTX) both in vitro and in vivo. Immunohistochemistry and FCM assays demonstrated that SPC-A1/DTX cells had a relatively higher rate of EGFR overexpression than SPC-A1 cells. Accordingly, SPC-A1/DTX cells were approximately 13.7 times resistant to DTX than SPC-A1 cells. The combined therapy of h-R3 and DTX showed strong synergistic suppressive effect on cell proliferation of SPC-A1/DTX cells in vitro. The synergistic antitumor effect was also observed in SPC-A1/DTX xenograft-bearing nude mice. Further study showed that h-R3 could lead to a significant cell arrest at G1 phase of cell cycle in both SPC-A1DTX and SPC-A1 cells. A dramatic increase of apoptosis rate was detected in h-R3-treated SPC-A1/DTX but not SPC-A1 cells. Moreover, when combined with DTX, h-R3 brought higher apoptosis rate in SPC-A1/DTX cells rather than in SPC-A1 cells. In conclusion, our results suggested that h-R3 could significantly enhance chemosensitivity of human lung adenocarcinoma cells to DTX, at least partially by induction of G1 phase arrest and cell apoptosis.
Hai-Zhu Song; Jun Yi; Jing Chen; Long-Bang Chen
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Oncology research     Volume:  20     ISSN:  0965-0407     ISO Abbreviation:  Oncol. Res.     Publication Date:  2012  
Date Detail:
Created Date:  2012-10-05     Completed Date:  2012-11-29     Revised Date:  2013-05-28    
Medline Journal Info:
Nlm Unique ID:  9208097     Medline TA:  Oncol Res     Country:  United States    
Other Details:
Languages:  eng     Pagination:  39-47     Citation Subset:  IM    
Department of Medical Oncology, Jinling Hospital, Medical School of Nanjing University, Nanjing, China.
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MeSH Terms
Adenocarcinoma / drug therapy*,  immunology
Adjuvants, Immunologic / therapeutic use*
Antibodies, Monoclonal, Humanized / therapeutic use*
Antineoplastic Agents / therapeutic use*
Cell Line, Tumor
Combined Modality Therapy
Drug Resistance, Neoplasm
Lung Neoplasms / drug therapy*,  immunology
Mice, Nude
Receptor, Epidermal Growth Factor / immunology
Taxoids / therapeutic use*
Xenograft Model Antitumor Assays
Reg. No./Substance:
0/Adjuvants, Immunologic; 0/Antibodies, Monoclonal, Humanized; 0/Antineoplastic Agents; 0/Taxoids; 0/nimotuzumab; 15H5577CQD/docetaxel; EC, Epidermal Growth Factor

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