Parishin B blocking TRIB3-AKT1 interaction inhibits breast cancer lung metastasis
Xiongtao Cheng1,2, Jianguo Sun3, Shouhong Chen4
1Graduate School, Hunan University of Chinese Medicine, Changsha, Hunan, China.
Background:
TRIB3 has been reported to mediate breast cancer (BC) proliferation and metastasis by interacting with AKT1, and blocking the interaction between TRIB3 and AKT1 can inhibit the progression of BC. Besides, inhibiting TRIB3 to turn "cold tumor" hot has also been proved to be an effective therapeutic strategy for BC. Thus, this study aim to find drugs that can bind to TRIB3 to inhibit BC progression, and further elucidate its mechanism.
Methods:
The possible inhibitors of TRIB3 were screened by high-throughput molecular docking, CETSA, and CO-IP assay. Then, the effect of TRIB3 inhibitor anti BC was assessed by CCK-8 assay, flow cytometry, plate colony formation assay, and transwell assay; and the RNA-seq was empolyed to study the potential mechanism of Parishin B (PB) anti-BC. Finally, the effect of TRIB3 inhibitor on BC lung metastasis in vivo was evaluated.
Results:
PB was screened as a possible inhibitor of TRIB3, and CETSA and CO-IP assay indicated that PB could target TRIB3 and block TRIB3-AKT1 interaction. In addition, PB exhibited good anti-BC activity without drug toxicity in normal breast cells by experiments in vitro, and RNA-seq analysis suggested PB could inhibit the proliferation and invasion of BC cells related with cell cycle. It was also proved that PB could inhibit BC lung metastasis in vivo.
Conclusion:
The study demonstrated PB can bind to TRIB3 to inhibit BC proliferation and lung metastasis by blocking TRIB3-AKT1 interaction and regulating cell cycle, providing a therapeutic agent for the treatment of BC.
Insights
Parishin B (PB) inhibits breast cancer (BC) progression by targeting TRIB3 and blocking its interaction with AKT1. This novel therapeutic agent also prevents BC lung metastasis and shows no toxicity in normal cells.
Area of Science:
- Oncology
- Molecular Biology
- Pharmacology
Background:
- Tribbles pseudokinase 3 (TRIB3) promotes breast cancer (BC) proliferation and metastasis via AKT1 interaction.
- Inhibiting TRIB3 is a strategy to enhance BC immunotherapy by converting
- cold tumors" to
- hot tumors".
Purpose of the Study:
- To identify drugs targeting TRIB3 for BC treatment.
- To elucidate the mechanism of TRIB3 inhibition in BC progression.
Main Methods:
- High-throughput molecular docking, CETSA, and CO-IP assays for inhibitor screening.
- In vitro assays (CCK-8, flow cytometry, colony formation, Transwell) to assess anti-BC activity.
- RNA-seq for mechanism elucidation and in vivo studies for metastasis evaluation.
Main Results:
- Parishin B (PB) identified as a TRIB3 inhibitor, blocking TRIB3-AKT1 interaction.
- PB demonstrated significant anti-BC activity in vitro without toxicity to normal cells.
- PB inhibited BC cell proliferation, invasion, and lung metastasis in vivo, linked to cell cycle regulation.
Conclusions:
- PB effectively inhibits BC proliferation and metastasis by targeting TRIB3-AKT1 interaction and regulating cell cycle.
- PB represents a promising therapeutic agent for breast cancer treatment.
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