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JOURNAL ARTICLE

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

Chenfei Zhou, Liangjun Zhu, Jun Ji, Fangmi Ding, Chao Wang, Qu Cai, Yingyan Yu, Zhenggang Zhu, Jun Zhang
Current Cancer Drug Targets 2017, 17 (1): 89-97
27739365

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.

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