Isocorydine decrease gemcitabine-resistance by inhibiting epithelial-mesenchymal transition via STAT3 in pancreatic...

Area of Science:

• Oncology
• Pharmacology
• Natural Products Chemistry

Background:

• Gemcitabine is a standard chemotherapy for pancreatic cancer but resistance limits efficacy.
• Pancreatic cancer cells develop gemcitabine resistance, leading to poor therapeutic outcomes.
• Isocorydine (ICD), a natural alkaloid, exhibits anti-cancer properties against various cell types.

Purpose of the Study:

• To investigate the synergistic effect of Isocorydine (ICD) and gemcitabine in pancreatic cancer.
• To elucidate the molecular mechanisms underlying the combination therapy's efficacy.
• To evaluate the therapeutic potential of ICD and gemcitabine in preclinical models.

Main Methods:

• Cell viability assays were performed on pancreatic cancer cells.
• Microarray analysis was used to identify molecular targets.
• STAT3 knockdown was conducted to assess its role in the synergistic effect.
• In vivo xenograft models were utilized to confirm therapeutic efficacy.

Main Results:

• ICD synergistically enhanced gemcitabine's inhibition of pancreatic cancer cell viability.
• ICD suppressed gemcitabine-induced upregulation of STAT3 and epithelial-mesenchymal transition (EMT).
• Knocking down STAT3 reduced the combination index of ICD and gemcitabine.
• ICD reversed gemcitabine-induced increases in EMT markers, inhibiting cell migration and invasion.
• Combination therapy demonstrated synergistic effects in preclinical xenograft models.

Conclusions:

• ICD and gemcitabine exhibit synergistic anti-cancer activity in pancreatic cancer.
• The combination therapy targets the STAT3/EMT pathway, overcoming gemcitabine resistance.
• ICD represents a promising therapeutic agent for combination treatment in pancreatic cancer.