DGG-100629 inhibits lung cancer growth by suppressing the NFATc1/DDIAS/STAT3 pathway

Area of Science:

• Oncology
• Molecular Biology
• Pharmacology

Background:

• DNA damage-induced apoptosis suppressor (DDIAS) is implicated in lung and liver cancer progression.
• Targeting DDIAS presents a potential therapeutic strategy for cancers.

Purpose of the Study:

• To identify novel anticancer agents that inhibit DDIAS transcription.
• To investigate the therapeutic potential of DGG-100629 in lung cancer, particularly gefitinib-resistant forms.

Main Methods:

• Chemical library screening to identify DDIAS inhibitors.
• In vitro assays using lung cancer cell lines to assess DGG-100629 effects on DDIAS expression, cell growth, and signaling pathways (JNK, NFATc1, STAT3).
• In vivo xenograft assays and analysis of patient-derived gefitinib-resistant cells.

Main Results:

• DGG-100629 suppressed lung cancer cell growth by inhibiting DDIAS expression.
• DGG-100629 activated JNK, inhibited NFATc1 nuclear translocation, and suppressed the STAT3 pathway.
• DGG-100629 demonstrated efficacy in xenograft models and in patient-derived gefitinib-resistant lung cancer cells.

Conclusions:

• DDIAS blockade is a promising therapeutic approach for lung cancer.
• DGG-100629 represents a novel therapeutic strategy for treating gefitinib-resistant lung cancer by targeting DDIAS, JNK, and STAT3 pathways.