Raltitrexed regulates proliferation and apoptosis of HGC-27 cells by upregulating RSK4
Related Experiment Video
Updated: Aug 30, 2025

Generation of Stable Human Cell Lines with Tetracycline-inducible Tet-on shRNA or cDNA Expression
Published on: March 5, 2013
Cong Hu1, Xinhua Chen1, Xu Lin2
1Department of General Surgery, Nanfang Hospital, Southern Medical University, No. 1929, Guangzhou Avenue North, Baiyun District, Guangzhou, 510515, China.
Background:
Raltitrexed is a specific inhibitor of thymidylate synthase and a potential chemotherapeutic agent for the treatment of advanced gastric cancer. In this study, we investigated the effect of raltitrexed on the proliferation of HGC-27 human gastric cancer cells and its potential underlying molecular mechanism(s).
Methods:
RT-qPCR and western blotting were used to quantify RSK4 levels. Colony formation and flow cytometry assays were used to assess HGC-27 cell proliferation, cell cycle progression, mitochondrial membrane potential, and apoptosis. The expression of cell cycle and apoptosis markers were determined by western blotting.
Results:
Our results demonstrate that raltitrexed upregulated RSK4 mRNA and protein levels in HGC-27 cells. Moreover, raltitrexed significantly inhibited tumor cell colony formation, arrested the cell cycle, decreased the mitochondrial membrane potential, and induced apoptosis. We observed that raltitrexed was capable of upregulating the expression of Bax, cyclin A1, and CDK3, and downregulating the expression of Bcl-2 and cleaved caspase-3. Importantly, siRNA-mediated RSK4 knockdown significantly reduced the inhibitory effect of raltitrexed on cell proliferation and its promotion of cell apoptosis. Moreover, silencing of RSK4 inhibited the raltitrexed-induced upregulation of cytochrome C. In addition, the changes in molecular markers related to the cell cycle and apoptosis induced by raltitrexed were reduced upon RSK4 depletion.
Conclusion:
Our study shows that RSK4 is a key target of raltitrexed in the regulation of gastric cancer cell proliferation, cell cycle progression, and apoptosis.
Related Concept Videos
Inhibition of Cdk Activity
mTOR Signaling and Cancer Progression
The mTOR pathway or the...
Abnormal Proliferation
Small GTPases - Ras and Rho
Three regulatory proteins control their activity:
The Ras Gene
Ras is a...
The Retinoblastoma Gene
The first-ever tumor suppressor gene called Rb was identified in retinoblastoma - a rare eye tumor in children. In inherited forms of the disease, a child inherits one defective copy of the Rb gene, which predisposes them to retinoblastoma. However,...

