Triptolide modulates tumour-colonisation and anti-tumour effect of attenuated Salmonella encoding DNase I

Area of Science:

• Oncology
• Microbiology
• Pharmacology

Background:

• Attenuated Salmonella strains face limitations in tumor suppression due to host immunity and toxicity.
• Engineered bacterial strains offer potential for novel cancer therapies.

Purpose of the Study:

• To evaluate the synergistic anti-melanoma effects of triptolide (TPL) and an engineered VNP20009-DNase I strain.
• To investigate the underlying molecular mechanisms of this combination therapy.

Main Methods:

• In vitro assessment of TPL effects on B16F10 melanoma cells (growth, migration, apoptosis).
• In vivo evaluation of TPL and VNP20009-DNase I combination therapy in a murine melanoma model.
• Analysis of key molecular markers including Bcl-2/Bax, Caspase-3, TLR4/NF-κB, and p-AKT/AKT signaling pathways.

Main Results:

• TPL inhibited melanoma cell growth and migration, and enhanced apoptosis in vitro.
• Combination therapy improved tumor colonization by VNP20009-DNase I and increased necrotic areas in vivo.
• Significant tumor volume suppression and prolonged survival were observed in mice treated with the combination therapy.
• The therapy modulated Bcl-2/Bax, Caspase-3, TLR4/NF-κB, and AKT signaling pathways, reducing pro-inflammatory factors.

Conclusions:

• TPL and VNP20009-DNase I exhibit potent synergistic anti-melanoma effects.
• This combination strategy represents a promising approach for cancer therapy, leveraging approved agents.