Investigation of the Anti-Lung Cancer Activity and Mechanism of Umbilical Cord Blood Stem Cell-Derived NK Cell Exosomes

Objective In order to determine the therapeutic efficacy and mechanism of action of natural killer cell-based exosomes from umbilical cord blood stem cells (UCB-NK-EXO) in a lung cancer model.Methods Cultured umbilical cord blood mononuclear cells (CBMCs) followed by IL-21 culture system to expand NK cells. All exosomes were isolated as well as obtained from the collected cell culture supernatant. The proliferation and apoptosis caused by UCB-NK-EXO to A549 lung cancer cells are observed by the CCK-8test and flow cytometry. Uptake by cells after exosome treatment was checked with confocal microscopy. A549 xenograft tumors were made in nude mice, and UCB-NK-EXO was given through the tail vein. The tumor growth happens and the liver & kidney in serum was checked for functions tests. I used western blot methodology to find out if there was a related-apoptosis signaling molecule in the tumor squads.Results UCB-NK-EXO greatly inhibited the proliferation of A549 cells (P <0.01), and promoted the apoptosis of the cells (P<0.001). It was also successfully internalized by the cells. The UCB-NK-EXO group had a much stronger anti-tumor effect than the DOX group in the in vivo experiments and also had a better effect on survival time p<0.001. UCB-NK-EXO treatment has no bodyweight loss and no hepatorenal toxicity of above Western blot results show cytotoxic protein like Granzyme B & Perforin exist in UCB-NK-EXO and Tumor tissue has very high expression of Apoptotic proteins like Caspase related proteins.Conclusion UCB-NK-EXO effectively inhibits the growth of A549 lung cancer both in vitro and in vivo. The mechanism involves the delivery of cytotoxic proteins to tumor cells, activation of the Caspase-dependent apoptosis pathway, and subsequent induction of tumor cell apoptosis. UCB-NK-EXO demonstrates superior antitumor efficacy and a more favorable safety profile compared to the conventional chemotherapeutic agent doxorubicin.