Cytotoxic effects of pemetrexed in gastric cancer cells

Jee Hyun Kim1, Keun-Wook Lee, Yeonjoo Jung

  • 1Department of Internal Medicine, Seoul National University College of Medicine, 28, Yongon-Dong, Chongno-Gu, Seoul.

Cancer Science
|June 17, 2005
PubMed

Insights

Pemetrexed shows significant cytotoxicity against gastric cancer cell lines, often exceeding 5-fluorouracil. Its combination with cisplatin demonstrates additive or synergistic effects, supporting clinical use, though sensitivity is not predicted by key gene expressions.

Area of Science:

  • Oncology
  • Pharmacology
  • Molecular Biology

Background:

  • Pemetrexed is a novel antifolate drug with demonstrated efficacy in various solid tumors.
  • Gastric cancer remains a significant global health challenge, necessitating novel therapeutic strategies.

Purpose of the Study:

  • To evaluate the cytotoxic effects of pemetrexed in gastric cancer cell lines.
  • To investigate the interaction between pemetrexed and cisplatin.
  • To identify potential genetic markers predicting pemetrexed sensitivity.

Main Methods:

  • Cytotoxicity assessed using MTT assay.
  • Drug interactions evaluated via isobologram analysis.
  • Gene expression analysis (protein and mRNA) for thymidylate synthase (TS), folylpoly-gamma-glutamate synthetase (FPGS), and reduced folate carrier (RFC1).

Main Results:

  • Pemetrexed exhibited greater cytotoxicity than 5-fluorouracil across tested gastric cancer cell lines.
  • The combination of pemetrexed and cisplatin displayed additive or synergistic interactions.
  • No significant correlation was found between TS, FPGS, or RFC1 expression levels (protein or mRNA) and pemetrexed sensitivity.

Conclusions:

  • Pemetrexed demonstrates significant activity against gastric cancer cell lines.
  • The combination therapy of pemetrexed and cisplatin warrants further clinical investigation for gastric cancer treatment.
  • Pemetrexed sensitivity in gastric cancer appears to be multifactorial, not predictable by the expression of TS, FPGS, or RFC1 alone.

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