辣椒素纳米颗粒使人肺鳞状细胞癌对紫杉醇的生长抑制活性增敏

Purpose of the Study: Squamous cell carcinoma of the lung (LUSC) develops in the central part of the lung, from cells lining the airways. It is characterized by rapid doubling time, aggressive clinical progression, and a dismal five-year survival rate. The first line treatment for LUSC includes a taxane with carboplatin and immunotherapy. The acquisition of resistance to paclitaxel is a major therapeutic challenge in human LUSCs. Several convergent studies show that nutritional phytochemicals can often improve the therapeutic response of chemotherapeutic drugs. The long-term objective of our laboratory is to identify dietary chemicals that may improve the anti-cancer activity of chemotherapeutic drugs. Our published data show that capsaicin (the spicy component of chili peppers) enhanced the pro-apoptotic activity of the chemotherapy drug camptothecin in human small-cell lung cancers. However, the feasibility of capsaicin as a potential anti-cancer drug is limited by its side effect profile. The administration of capsaicin produces heat sensation, GI irritation, stomach cramps, and nausea. A way to overcome these hurdles is to encapsulate capsaicin into sustained release polymeric systems. The objective of the present research project was to explore the combinatorial activity of Capsaicin [poly(lactic-co-glycolic acid)] nanoparticles (hereby called CAP-PLGA-NPs] and paclitaxel in human LUSCs. Experimental Procedures : The pro-apoptotic activity of the combination of paclitaxel and CAP-PLGA-NPs was evaluated by Caspase-3 Activity Assays and Cell Death ELISA assays. We also determined the ability of the combination of paclitaxel and CAP-PLGA-NPs to inhibit anchorage-dependent growth using soft agar assay. Chou-Talalay isobologram analysis was used to determine whether the interaction between the two drugs was additive or synergistic. Results : CAP-PLGA-NPs sensitized human LUSC cells towards the growth-inhibitory activity of paclitaxel Conclusions : The administration of CAP-PLGA-NPs may enhance the growth-suppressive activity of paclitaxel in human LUSCs.