4.4 Article

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

Journal

CURRENT CANCER DRUG TARGETS
Volume 17, Issue 1, Pages 89-97

Publisher

BENTHAM SCIENCE PUBL LTD
DOI: 10.2174/1568009616666161013101657

Keywords

Pancreatic cancer; nimotuzumab; predictive marker; EGFR; KRAS mutation

Categories

Funding

  1. National Science Foundation of China [81672327, 81372644, 81372645]
  2. FONG SHU FOOK TONG Foundation
  3. National Key Clinical Discipline (Oncology)
  4. innovation foundation of translational medicine of Shanghai Jiao Tong University School of Medicine [15ZH1002, 15ZH3001, 15ZH4001]
  5. Program for Outstanding Medical Academic Leader
  6. Shanghai Municipal Education Commission-Gaofeng Clinical Medicine Grant Support [20161410]

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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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