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.