Oridonin-induced mitochondria-dependent apoptosis in esophageal cancer cells by inhibiting PI3K/AKT/mTOR and Ras/Raf...

Area of Science:

• Pharmacology
• Oncology
• Molecular Biology

Background:

• Oridonin, a diterpenoid from Rabdosia rubescens, exhibits known antitumor properties.
• The specific effects of oridonin on human esophageal cancer require elucidation.

Purpose of the Study:

• To investigate the efficacy of oridonin against human esophageal cancer cells in vitro and in vivo.
• To explore the underlying molecular mechanisms of oridonin's anticancer effects.

Main Methods:

• In vitro studies using esophageal cancer cell lines (KYSE-30, KYSE-150, EC9706) to assess proliferation, cell cycle, and apoptosis.
• Western blot analysis to evaluate key proteins involved in cell cycle regulation, apoptosis, and signaling pathways (PI3K/Akt/mTOR, Ras/Raf).
• In vivo studies using a human esophageal cancer xenograft mouse model to evaluate tumor growth inhibition.

Main Results:

• Oridonin suppressed esophageal cancer cell proliferation, induced cell cycle arrest, and promoted mitochondrial-mediated apoptosis in a dose-dependent manner.
• Oridonin modulated cell cycle regulators (downregulated cyclin B1, CDK2; upregulated p53, p21) and apoptosis markers (increased Bax, decreased Bcl-2, elevated cleaved caspases).
• Oridonin inhibited the PI3K/Akt/mTOR and Ras/Raf signaling pathways and significantly reduced tumor growth in vivo.

Conclusions:

• Oridonin demonstrates significant anticancer activity against human esophageal cancer cells.
• Oridonin exerts its effects by inducing cell cycle arrest, apoptosis, and inhibiting key signaling pathways.
• Oridonin represents a potential therapeutic candidate for esophageal cancer treatment.