The therapeutic potential of a novel non-ATP-competitive fibroblast growth factor receptor 1 inhibitor on gastric cancer

Chaochao Xu, Wulan Li, Peihong Qiu, Yiqun Xia, Xiaojing Du, Fen Wang, Lailai Shen, Qiuxiang Chen, Yunjie Zhao, Rong Jin, Jianzhang Wu, Guang Liang, Xiaokun Li

Research output: Contribution to journalArticlepeer-review

9 Scopus citations


Previous studies showed that fibroblast growth factor receptor 1 (FGFR1) is an attractive target in gastric cancer therapy. In the current study, we aimed to investigate whether the compound L6123, a novel non-ATP-competitive FGFR1 inhibitor, could show better antitumor activity than the leading compound, nordihydroguaiaretic acid (NDGA), in FGFR1-overexpressing gastric cancer cells. Using an MTT assay, we investigated the inhibitory effect of L6123 on the viability of three gastric cancer cells (MGC-803, SGC-7901, and BGC-823) overexpressing FGFR1, wild-type mouse embryonic fibroblast (MEF-WT), and MEF expressing FGFR1, FGFR2, and FRS2 gene knockout (MEF-FGFR1-FGFR2-FRS2-ko). We studied the antitumor mechanism of L6123 against the gastric cancer cell line SGC-7901 by western blot analysis. The antitumor effects of L6123 on the gastric cancer cell line SGC-7901 were detected by flow cytometry, Hoechst staining, western blot analysis, and Transwell invasion assay. L6123 had lower IC50 in all three gastric cancer cells than NDGA and showed better inhibitory activity against MEF-WT cells than against MEF-FGFR1-FGFR2-FRS2-ko cells. In the SGC-7901 gastric cell, L6123 inhibited the FGF2-induced phosphorylation of FGFR1FRS2ERK12 in a dose-dependent manner, induced the activation of the apoptosis-related proteins, cleaved-PARP and cleaved-caspase-3, decreased the expression of pro-caspase-3 and Bcl-2, and induced tumor cell apoptosis. L6123 also dose-dependently reduced cell invasion ability, and showed better activity than NDGA at the same concentration. A novel non-ATP-competitive inhibitor L6123 showed excellent antigastric cancer activity by inhibiting the FGFR1 signaling pathway. Thus, we discovered a potential agent for the treatment of FGFR1-overexpressing gastric cancer.

Original languageEnglish (US)
Pages (from-to)379-387
Number of pages9
JournalAnti-Cancer Drugs
Issue number4
StatePublished - Apr 2015


  • fibroblast growth factor receptor 1
  • gastric cancer
  • molecular targeted therapy

ASJC Scopus subject areas

  • Medicine(all)


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