Inhibiting STAT3 and Activating TLR Against Tumors With OPSS Liposomes, Curcumin, and TLR Agonists
DOI:
https://doi.org/10.47611/jsrhs.v10i1.1362Keywords:
Cancer, Curcumin, Toll-Like Receptors, STAT3 Pathway, Liposomes, Complement C3, TLR, TLR Agonists, Macrophage, TumorAbstract
In solid malignancies such as breast cancer, the tumor cells create an immunosuppressive environment through the aid of macrophages. The macrophages become tumor-associated and inhibit a T-cell response critical to removing the cancerous cells. The main signaling pathway responsible for the macrophages’ pro-tumoral behavior is the STAT3 signaling pathway, a subset of the JAK/STAT signaling pathway that prevents the toll-like receptor (TLR) expression. TLRs are essential to the immune system's anti-tumoral response. Therefore, to repolarize the macrophages in from a pro-tumoral to an anti-tumoral form, curcumin (STAT3 inhibitor), and TLR agonists (TLR stimulant) were delivered to a co-culture using complement C3 liposomes (OPSS liposomes). The OPSS liposomes cause macrophages to uptake the liposomes, allowing for targeted drug delivery to macrophages. 4T1 cancer cells and BMDMs were co-cultured and treated with control liposomes containing PBS, OPSS liposomes containing curcumin and TLR agonist, and OPSS liposomes containing TLR agonist. RT-qPCR measured gene expression, and flow cytometry measured protein expression. This study’s results point to the effectiveness of the OPSS liposome, curcumin, and TLR agonist treatment. The combination of curcumin and TLR agonist appear to effectively inhibit the STAT3 signaling pathway and activate the expression of TLR. Future studies should implement the OPSS liposome, curcumin, and TLR agonist treatment in a mouse model and observe for a potential T-cell response.
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