Related Experiment Video
Updated: Aug 17, 2026

Multi-Gene Single Nucleotide Polymorphism Detection in Gastric Cancer Based on Ion Semiconductor Sequencing Platform
Published on: May 10, 2024
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.
Abstract:
Pemetrexed is a newly developed multitargeted antifolate with promising clinical activity in many solid tumors including gastric cancer. The aim of the present study was to evaluate the cytotoxicity of pemetrexed and its mode of interaction with cisplatin in gastric cancer cell lines, and to identify genes associated with sensitivity to pemetrexed. The cytotoxic activity of pemetrexed was assessed by tetrazolium-based colorimetric assay (MTT assay) and the interaction between pemetrexed and cisplatin was evaluated by the isobologram method. Western immunoblotting and real time RT-PCR analysis of thymidylate synthase (TS), folylpoly-gamma-glutamate synthetase (FPGS) and reduced folate carrier (RFC1) were performed in order to determine whether sensitivity to pemetrexed would be predictable by protein or mRNA expression levels. Pemetrexed was more cytotoxic than 5-fluorouracil, with IC50 between 17 and 310 nM in most of the gastric cancer cell lines examined and the pemetrexed/cisplatin combination resulted in additive or synergistic interaction. The protein expressions of TS, FPGS, and RFC1 were significantly associated with IC50 for 5-fluorouracil, but no such association was found for pemetrexed chemosensitivity. The mRNA expressions of RFC1, FPGS and other target and resistance related genes revealed no significant association with pemetrexed sensitivity. In conclusion, pemetrexed is active against gastric cancer cell lines and the pemetrexed/cisplatin combination showed a synergistic or additive interaction, supporting its clinical use in gastric cancer. Drug sensitivity toward pemetrexed could not be predicted by the expressions of TS, RFC1, or FPGS and we suggest that it is determined by interactions between multiple genes.
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.
Related Concept Videos
Targeted Cancer Therapies
There are several types of targeted therapies against specific...
Mitogens and the Cell Cycle
Gastritis II: Pathophysiology
