Triptolide Reduces MDA-MB-231 Cell Metastasis by Attenuating Epithelial-Mesenchymal Transition through the...

Area of Science:

• Oncology
• Molecular Biology
• Natural Products Chemistry

Background:

• Triple-negative breast cancer (TNBC) is an aggressive subtype with poor prognosis due to high metastasis rates.
• Triptolide, a natural diterpene trioxide, exhibits potential anti-tumor properties.
• Understanding the mechanisms of TNBC metastasis is crucial for developing effective treatments.

Purpose of the Study:

• To investigate the metastatic inhibitory effects of triptolide on MDA-MB-231 TNBC cells.
• To elucidate the underlying molecular mechanisms of triptolide's action.
• To identify triptolide as a potential therapeutic agent for TNBC.

Main Methods:

• Cell proliferation, apoptosis, migration, and invasion assays were performed on MDA-MB-231 cells treated with triptolide.
• Western blotting and qRT-PCR were used to analyze protein and mRNA expression levels of key metastatic markers (ROCK1, p-Akt, N-cadherin, vimentin, MMP-9, PTEN, E-cadherin).
• Molecular docking and ROCK1 inhibition studies with Y27632 were conducted to confirm the target.

Main Results:

• Triptolide suppressed proliferation and induced apoptosis in MDA-MB-231 cells in a dose- and time-dependent manner.
• Low doses of triptolide significantly reduced MDA-MB-231 cell migration and invasion.
• Triptolide modulated the expression of key EMT markers, decreasing ROCK1, p-Akt, N-cadherin, vimentin, and MMP-9, while increasing PTEN and E-cadherin. ROCK1 was identified as a primary target.

Conclusions:

• Triptolide effectively inhibits the proliferation, migration, and invasion of MDA-MB-231 TNBC cells.
• Triptolide exerts its anti-metastatic effects by inducing apoptosis and inhibiting epithelial-mesenchymal transition (EMT) via ROCK1 signaling.
• Triptolide represents a promising therapeutic candidate for targeting metastatic TNBC.