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Sorafenib inhibits 5-fluorouracil-resistant gastric cancer cell growth

Hee Man Kim1,2, Sun A Kim1, Soo Been Park1

  • 1a Division of Gastroenterology, Department of Internal Medicine and Yonsei Institute of Gastroenterology , Yonsei University College of Medicine , Seoul , Republic of Korea.

Scandinavian Journal of Gastroenterology
|January 24, 2017
PubMed
Abstract

Insights

Sorafenib combined with 5-fluorouracil (5-FU) effectively inhibited gastric cancer growth in models, overcoming resistance. This combination therapy shows promise for treating advanced gastric cancer.

Area of Science:

  • Oncology
  • Pharmacology
  • Cancer Research

Background:

  • Sorafenib, a multi-kinase inhibitor, is utilized in diverse cancer treatments.
  • Gastric cancer often develops resistance to conventional chemotherapy, such as 5-fluorouracil (5-FU).
  • Investigating novel therapeutic strategies to overcome chemoresistance in gastric cancer is crucial.

Purpose of the Study:

  • To evaluate the inhibitory effects of sorafenib on gastric cancer xenograft models.
  • To assess the efficacy of sorafenib in combination with 5-FU against 5-FU-resistant gastric cancer cells.
  • To determine sorafenib's impact on cancer cell proliferation and sphere formation in resistant models.

Main Methods:

  • Determined the half-maximal inhibitory concentration (IC50) of sorafenib in NCI-N87 gastric cancer cells.
  • Established xenograft models in BALB/c nude mice, treating with vehicle, sorafenib, 5-FU, or a combination.
  • Developed 5-FU-resistant NCI-N87 cells through repeated drug exposure for in vitro and in vivo studies.

Main Results:

  • Sorafenib demonstrated dose-dependent inhibition of NCI-N87 cell growth (IC50 ≈ 16.35 μM) and reduced MAPK pathway phosphorylation.
  • The combination of sorafenib and 5-FU significantly inhibited xenograft tumor growth more than monotherapy (p < 0.05).
  • Sorafenib effectively suppressed proliferation and sphere formation in both parental and 5-FU-resistant NCI-N87 cells.

Conclusions:

  • The combination of sorafenib and 5-FU exhibits synergistic antitumor activity in gastric cancer xenografts.
  • Sorafenib demonstrates potential in overcoming 5-FU resistance by inhibiting resistant cell proliferation and sphere formation.
  • These findings support sorafenib as a valuable agent to enhance conventional chemotherapy efficacy in gastric cancer treatment.
Keywords:
5-fluorouracilGastric cancerdrug resistanceneoplastic stem cellsorafenibsphere formation

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