摘要
背景:尼妥珠单抗已显示治疗晚期胰腺癌的是有效的,但尚未建立预测指标。 目的:探讨EGFR和KRAS基因状态对尼妥珠单抗的抗肿瘤的疗效的影响并探讨其作用机制。 方法:用Western blot和免疫细胞化学法分析胰腺癌细胞株BxPC3,Panc-1和Patu-8988的EGFR表达,并基因测序确定KRAS基因状态。在体内外评价尼妥珠单抗的抗肿瘤作用。用Western blot、免疫组化分析,和/或实时PCR分析EGFR信号通路相关分子和IL-6的的表达。 结果:BxPC3细胞有野生型KRAS和高水平EGFR;Panc-1细胞有突变的KRAS基因(G13A)和底水平的EGFR;Patu-8988细胞有突变的KRAS (G12V) and 高水平 EGFR。在体外尼妥珠单抗对细胞增殖或凋亡无影响。与对照组比较,尼妥珠单抗明显抑制BxPC3和Patu-8988异种移植的生长,而不针对Panc-1的异种移植。尼妥珠单抗明显减少BxPC3和Patu-8988异种移植里的EGFR表达。对照组里BxPC3和Patu-8988异种移植的IL-6表达高于Panc-1的异种移植,尼妥珠单抗明显减少其表达水平。 结论:在体内胰腺癌细胞的EGFR高表达对尼妥珠单抗更敏感。KRAS基因状态对尼妥珠单抗治疗胰腺癌细胞的疗效没有影响。
关键词: 胰腺癌,尼妥珠单抗,预测指标,EGFR,KRAS基因突变。
图形摘要
Current Cancer Drug Targets
Title:EGFR High Expression, but not KRAS Status, Predicts Sensitivity of Pancreatic Cancer Cells to Nimotuzumab Treatment In Vivo
Volume: 17 Issue: 1
Author(s): Chenfei Zhou, Liangjun Zhu, Jun Ji, Fangmi Ding, Chao Wang, Qu Cai, Yingyan Yu, Zhenggang Zhu, Jun Zhang
Affiliation:
关键词: 胰腺癌,尼妥珠单抗,预测指标,EGFR,KRAS基因突变。
摘要: Background: Nimotuzumab is shown to be efficacious in advanced pancreatic cancer treatment, but its predictive marker has not been established.
Objective: To investigate the impact of EGFR and KRAS status on antitumor efficacy of nimotuzumab and to explore its underlying mechanism. Methods: EGFR expressions of pancreatic cancer cell lines, BxPC3, Panc-1, and Patu-8988, were analyzed by Western blot and immunocytochemistry, and KRAS status was determined by gene sequencing. Anti-tumor effect of nimotuzumab were evaluated in vitro and in vivo. The expressions of related molecules in EGFR pathway and IL-6 was analyzed by Western blot, immunohistochemistry, and/or real-time PCR. Results: BxPC3 cells had wild type KRAS and high-level EGFR; Panc-1 cells had mutant KRAS (G13A) and low-level EGFR; Patu-8988 cells had mutant KRAS (G12V) and high-level EGFR. Nimotuzumab did not affect cell proliferation or apoptosis in vitro. Growth of BxPC3 and Patu-8988 xenografts were significantly inhibited by nimotuzumab, but not Panc-1 xenografts, compared with that of the control group. Expression of EGFR in BxPC3 and Patu-8988 xenografts was significantly reduced by nimotuzumab. The IL-6 expression in BxPC3 and Patu-8988 xenografts was higher than that in Panc-1 xenografts in the control group, and was significantly reduced by nimotuzumab. Conclusion: Pancreatic cancer cells with EGFR high expression were more sensitive to nimotuzumab in vivo. KRAS status had no impact on anti-tumor efficacy of nimotuzumab in pancreatic cancer cells.Export Options
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Cite this article as:
Chenfei Zhou, Liangjun Zhu, Jun Ji, Fangmi Ding, Chao Wang, Qu Cai, Yingyan Yu, Zhenggang Zhu, Jun Zhang , EGFR High Expression, but not KRAS Status, Predicts Sensitivity of Pancreatic Cancer Cells to Nimotuzumab Treatment In Vivo, Current Cancer Drug Targets 2017; 17 (1) . https://dx.doi.org/10.2174/1568009616666161013101657
DOI https://dx.doi.org/10.2174/1568009616666161013101657 |
Print ISSN 1568-0096 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-5576 |
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