EGFR High Expression, but not KRAS Status, Predicts Sensitivity of Pancreatic Cancer Cells to Nimotuzumab Treatment In Vivo

Author(s): Chenfei Zhou, Liangjun Zhu, Jun Ji, Fangmi Ding, Chao Wang, Qu Cai, Yingyan Yu, Zhenggang Zhu, Jun Zhang

Journal Name: Current Cancer Drug Targets

Volume 17 , Issue 1 , 2017

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Graphical Abstract:


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.

Keywords: Pancreatic cancer, nimotuzumab, predictive marker, EGFR, KRAS mutation.

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Article Details

Year: 2017
Page: [89 - 97]
Pages: 9
DOI: 10.2174/1568009616666161013101657
Price: $65

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