title: Nimotuzumab increases chemosensitivity of human lung adenocarcinoma cell lines to docetaxel.
abstract: 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.
authors.affiliation: Department of Medical Oncology, Jinling Hospital, Medical School of Nanjing University, Nanjing, China.
authors.forename: Hai-Zhu
authors.initials: HZ
authors.lastname: Song
authors.forename: Jun
authors.initials: J
authors.lastname: Yi
authors.forename: Jing
authors.initials: J
authors.lastname: Chen
authors.forename: Long-Bang
authors.initials: LB
authors.lastname: Chen
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy* / Q000276:immunology; D000276:Adjuvants, Immunologic / Q000627:therapeutic use*; D000818:Animals; D061067:Antibodies, Monoclonal, Humanized / Q000627:therapeutic use*; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D045744:Cell Line, Tumor; D003131:Combined Modality Therapy; D000077143:Docetaxel; D019008:Drug Resistance, Neoplasm; D066246:ErbB Receptors / Q000276:immunology; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000276:immunology; D051379:Mice; D008819:Mice, Nude; D043823:Taxoids / Q000627:therapeutic use*; D023041:Xenograft Model Antitumor Assays
chemical_list: D000276:Adjuvants, Immunologic; D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents; D043823:Taxoids; D000077143:Docetaxel; C501466:nimotuzumab; D066246:ErbB Receptors