Cetuximab and Cisplatin Show Different Combination Effect in Nasopharyngeal Carcinoma Cells Lines via Inactivation of EGFR/AKT Signaling Pathway.
Cetuximab and Cisplatin Show Different Combination Effect in Nasopharyngeal Carcinoma Cells Lines via Inactivation of EGFR/AKT Signaling Pathway.
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DOI：
10.1155/2016/7016907
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发表时间：
2016
影响因子：
3
通讯作者：
He X
中科院分区：
文献类型：
--
作者：
Gu J;Yin L;Wu J;Zhang N;Huang T;Ding K;Cao H;Xu L;He X
鼻咽癌（Nasopharyngeal carcinoma，NPC）是我国南方常见的恶性肿瘤。顺铂是用于NPC治疗的经典化学治疗剂。尽管使用以顺铂为基础的同步放化疗，但远处转移失败仍令临床医生困惑，转移性NPC的结局仍令人失望。因此，对于这种癌症需要有效的全身治疗。表皮生长因子受体（EGFR）是肿瘤治疗的新靶点。我们预测，将传统的细胞毒性药物顺铂与新型分子靶向药物西妥昔单抗结合，对NPC细胞表现出较强的抗肿瘤作用。在本研究中，我们选择了HNE 1和CNE 2细胞，这已被证明具有不同的EGFR表达水平，以验证我们的猜想。两药方案在HNE 1细胞中显示出显著的协同作用，但在CNE 2细胞中显示出相加作用。我们的研究结果表明，顺铂诱导的细胞凋亡显着增强西妥昔单抗在高表达EGFR的HNE 1细胞，但在CNE 2细胞。进一步的分子机制研究表明，EGFR/AKT通路可能在细胞凋亡中起重要作用，并可能通过内源性途径介导HNE 1和CNE 2细胞的凋亡，从而导致该双药方案对HNE 1和CNE 2细胞的抗肿瘤作用不同。因此，该方案可以应用于个性化NPC治疗。
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.