Cetuximab and Cisplatin Show Different Combination Effect in Nasopharyngeal Carcinoma Cells Lines via Inactivation of EGFR/AKT Signaling Pathway
Nasopharyngeal carcinoma (NPC) is a common malignant cancer in South China. Cisplatin is a classical chemotherapeutic employed for NPC treatment. Despite the use of cisplatin-based concurrent chemoradiotherapy, distant failure still confuses clinicians and the outcome of metastatic NPC remains disap...
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| Format: | Article |
| Language: | English |
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Wiley
2016-01-01
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| Series: | Biochemistry Research International |
| Online Access: | http://dx.doi.org/10.1155/2016/7016907 |
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| author | Jiajia Gu Li Yin Jing Wu Nan Zhang Teng Huang Kai Ding Haixia Cao Lin Xu Xia He |
| author_facet | Jiajia Gu Li Yin Jing Wu Nan Zhang Teng Huang Kai Ding Haixia Cao Lin Xu Xia He |
| author_sort | Jiajia Gu |
| collection | DOAJ |
| description | Nasopharyngeal carcinoma (NPC) is a common malignant cancer in South China. Cisplatin is a classical chemotherapeutic employed for NPC treatment. Despite the use of cisplatin-based concurrent chemoradiotherapy, distant failure still confuses clinicians and the outcome of metastatic NPC remains disappointing. Hence, a potent systemic therapy is needed for this cancer. Epidermal growth factor receptor (EGFR) represents a promising new therapeutic target in cancer. We predicted that combining the conventional cytotoxic drug cisplatin with the novel molecular-targeted agent cetuximab demonstrates a strong antitumor effect on NPC cells. In this study, we selected HNE1 and CNE2 cells, which have been proved to possess different EGFR expression levels, to validate our conjecture. The two-drug regimen showed a significant synergistic effect in HNE1 cells but an additive effect in CNE2 cells. Our results showed that cisplatin-induced apoptosis was significantly enhanced by cetuximab in the high EGFR-expressing HNE1 cells but not in CNE2 cells. Further molecular mechanism study indicated that the EGFR/AKT pathway may play an important role in cell apoptosis via the mitochondrial-mediated intrinsic pathway and lead to the different antitumor effects of this two-drug regimen between HNE1 and CNE2 cells. Thus, the regimen may be applied in personalized NPC treatments. |
| format | Article |
| id | doaj-art-aa845fac860a4fcbb40c57923f8a9d90 |
| institution | Kabale University |
| issn | 2090-2247 2090-2255 |
| language | English |
| publishDate | 2016-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Biochemistry Research International |
| spelling | doaj-art-aa845fac860a4fcbb40c57923f8a9d902025-08-20T03:39:33ZengWileyBiochemistry Research International2090-22472090-22552016-01-01201610.1155/2016/70169077016907Cetuximab and Cisplatin Show Different Combination Effect in Nasopharyngeal Carcinoma Cells Lines via Inactivation of EGFR/AKT Signaling PathwayJiajia Gu0Li Yin1Jing Wu2Nan Zhang3Teng Huang4Kai Ding5Haixia Cao6Lin Xu7Xia He8The Fourth Clinical School of Nanjing Medical University, Nanjing 210009, ChinaThe Fourth Clinical School of Nanjing Medical University, Nanjing 210009, ChinaDepartment of Radiation Oncology, Nanjing Medical University Affiliated Jiangsu Cancer Hospital and Jiangsu Institute of Cancer Research, Nanjing 210009, ChinaThe Fourth Clinical School of Nanjing Medical University, Nanjing 210009, ChinaThe Fourth Clinical School of Nanjing Medical University, Nanjing 210009, ChinaDepartment of Radiation Oncology, Nanjing Medical University Affiliated Jiangsu Cancer Hospital and Jiangsu Institute of Cancer Research, Nanjing 210009, ChinaJiangsu Key Laboratory of Molecular and Translational Cancer Research, Nanjing, ChinaDepartment of Thoracic Surgery, Nanjing Medical University Affiliated Jiangsu Cancer Hospital and Jiangsu Institute of Cancer Research, Nanjing 210009, ChinaThe Fourth Clinical School of Nanjing Medical University, Nanjing 210009, ChinaNasopharyngeal carcinoma (NPC) is a common malignant cancer in South China. Cisplatin is a classical chemotherapeutic employed for NPC treatment. Despite the use of cisplatin-based concurrent chemoradiotherapy, distant failure still confuses clinicians and the outcome of metastatic NPC remains disappointing. Hence, a potent systemic therapy is needed for this cancer. Epidermal growth factor receptor (EGFR) represents a promising new therapeutic target in cancer. We predicted that combining the conventional cytotoxic drug cisplatin with the novel molecular-targeted agent cetuximab demonstrates a strong antitumor effect on NPC cells. In this study, we selected HNE1 and CNE2 cells, which have been proved to possess different EGFR expression levels, to validate our conjecture. The two-drug regimen showed a significant synergistic effect in HNE1 cells but an additive effect in CNE2 cells. Our results showed that cisplatin-induced apoptosis was significantly enhanced by cetuximab in the high EGFR-expressing HNE1 cells but not in CNE2 cells. Further molecular mechanism study indicated that the EGFR/AKT pathway may play an important role in cell apoptosis via the mitochondrial-mediated intrinsic pathway and lead to the different antitumor effects of this two-drug regimen between HNE1 and CNE2 cells. Thus, the regimen may be applied in personalized NPC treatments.http://dx.doi.org/10.1155/2016/7016907 |
| spellingShingle | Jiajia Gu Li Yin Jing Wu Nan Zhang Teng Huang Kai Ding Haixia Cao Lin Xu Xia He Cetuximab and Cisplatin Show Different Combination Effect in Nasopharyngeal Carcinoma Cells Lines via Inactivation of EGFR/AKT Signaling Pathway Biochemistry Research International |
| title | Cetuximab and Cisplatin Show Different Combination Effect in Nasopharyngeal Carcinoma Cells Lines via Inactivation of EGFR/AKT Signaling Pathway |
| title_full | Cetuximab and Cisplatin Show Different Combination Effect in Nasopharyngeal Carcinoma Cells Lines via Inactivation of EGFR/AKT Signaling Pathway |
| title_fullStr | Cetuximab and Cisplatin Show Different Combination Effect in Nasopharyngeal Carcinoma Cells Lines via Inactivation of EGFR/AKT Signaling Pathway |
| title_full_unstemmed | Cetuximab and Cisplatin Show Different Combination Effect in Nasopharyngeal Carcinoma Cells Lines via Inactivation of EGFR/AKT Signaling Pathway |
| title_short | Cetuximab and Cisplatin Show Different Combination Effect in Nasopharyngeal Carcinoma Cells Lines via Inactivation of EGFR/AKT Signaling Pathway |
| title_sort | cetuximab and cisplatin show different combination effect in nasopharyngeal carcinoma cells lines via inactivation of egfr akt signaling pathway |
| url | http://dx.doi.org/10.1155/2016/7016907 |
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