| 顾佳佳,尹 丽,吴 婧.西妥昔单抗体外协同增加顺铂对人鼻咽癌细胞株的抗肿瘤作用[J].中国肿瘤,2016,25(4):303-308. |
| 西妥昔单抗体外协同增加顺铂对人鼻咽癌细胞株的抗肿瘤作用 |
| Inhibitory Effect of Cetuximab Combined with Cisplatin on Nasopharyngeal Carcinoma Cell Lines and its Molecular Mechanism |
| 投稿时间：2015-10-16 |
| DOI：10.11735/j.issn.1004-0242.2016.04.A012 |
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| 中文关键词: 鼻咽癌 表皮生长因子受体 西妥昔单抗 顺铂 |
| 英文关键词:nasopharyngeal carcinoma epidermal growth factor receptor cetuximab cisplatin |
| 基金项目:江苏省科技厅临床医学重点专项（BL2014091） |
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| 中文摘要: |
| 摘 要：［目的］研究西妥昔单抗(Cetuximab，C225)联合顺铂(Cisplatin，DDP)对人鼻咽癌(nasopharyngeal carcinoma，NPC)细胞增殖和凋亡的影响及其分子机制。［方法］ 采用人鼻咽癌HNE1和CNE2细胞株，RT-qPCR检测表皮生长因子受体（epidermal growth factor receptor，EGFR）mRNA的差异性表达。实验分为对照组、西妥昔单抗组、顺铂组、两药联合组，采用CCK-8法、平板克隆形成实验检测细胞增殖能力，并评价药物的协同效应。流式细胞术检测各组细胞的凋亡情况。Western Blot检测AKT、p-AKT以及凋亡相关蛋白Bax、caspase-3、cleaved caspase-3的表达水平。［结果］药物持续作用48h后，两株细胞中两药联合组与单药组相比，均不同程度地提高对细胞的抑制率。在HNE1和CNE2细胞株中，两药协同指数分别为0.6和0.9。HNE1和CNE2细胞中EGFR mRNA分别呈现相对高表达和相对低表达状态。流式细胞术结果显示：HNE1细胞中，联合组的凋亡细胞比率显著性高于单药组，另外，两药联合作用更有效地下调了HNE1中凋亡蛋白Bax、caspase-3、cleaved caspase-3的表达，同时下调了EGFR/AKT信号通路关键蛋白AKT磷酸化表达。 ［结论］西妥昔单抗可能通过抑制顺铂介导的EGFR/AKT通路的磷酸化活化，产生协同抑制HNE1细胞增殖效应。两药联合在HNE1和CNE2细胞中的差异性效应为鼻咽癌的临床个体化治疗研究提供依据。 |
| 英文摘要: |
| Abstract：［Purpose］ To study the effect of cetuximab combined with cisplain on proliferation and apoptosis of nasopharyngeal carcinoma(NPC) cell lines CNE-2 and HNE-1 and its molecular mechanism. ［Methods］Nasopharyngeal carcinoma cell lines CNE-2 and HNE-1 were divided into contrast group，cetuximab group，cisplain group and combination group. The levels of epidermal growth factor receptor (EGFR) mRNA were detected by RT-qPCR. Cell counting Kits-8 (CCK-8) assay and colony formation assay were used to detect the proliferation viability and evaluate combination effect. Flow cytometry was used to determine apoptosis rate，and Western Blot was used to detect the protein expression level changes of Bax，caspase-3，cleaved caspase-3，AKT and p-AKT when cells were given different treatments. ［Results］ After treatment of 48h，the inhibitory rate of combination group were significantly higher than the monotherapy group in both cell lines. The combination index of HNE1 and CNE2 cells is 0.6 and 0.9，respectively. EGFR mRNA in HNE1 showed a relative high level，but a relative low level in CNE2 cells. Flow cytometry results showed that the apoptosis rate of combination group was significantly higher than the monotherapy group in HNE1 cells. Moreover，in HNE1 cells，the levels of Bax，caspase-3，cleaved caspase-3 protein of combination group were up-regulated more effectively than the monotherapy group. The level of p-AKT protein was significantly down-regulated in the combination group simultaneously. ［Conclusion］ Cetuximab and cisplatin show a synergism effect in HNE1 cells via inhibitory of EGFR/AKT signaling pathway phosphorylation activation. The different effect of the combination strategy on both HNE1 and CNE2 cell lines provides an evidence for individual treatment of NPC. |
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