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  • Delivery of human natural killer cell-derived exosomes for liver cancer therapy: an in vivo study in subcutaneous and orthotopic animal models.

Delivery of human natural killer cell-derived exosomes for liver cancer therapy: an in vivo study in subcutaneous and orthotopic animal models.

Drug delivery (2022-09-08)
Ho Yong Kim, Hyun-Ki Min, Hyeong-Woo Song, Ami Yoo, Seonmin Lee, Kyu-Pyo Kim, Jong-Oh Park, You Hee Choi, Eunpyo Choi
ABSTRACT

Exosomes are nanosized extracellular vesicles secreted by various cell types, including those of the immune system, such as natural killer (NK) cells. They play a role in intercellular communication by transporting signal molecules between the cells. Recent studies have reported that NK cell-derived exosomes (NK-exo) contain cytotoxic proteins-induced cell death. However, the characteristics and potential functions of NK-exo, especially for the liver cancer are poorly understood. In this study, we investigated the anti-tumor effects of NK-exo in the primary liver cancer, hepatocellular carcinoma (HCC), using the orthotopic and subcutaneous tumor model. We found that NK-exo expressed both typical exosomal markers (e.g. CD63, CD81, and Alix) and cytotoxic proteins (e.g. perforin, granzyme B, FasL, and TRAIL). NK-exo were selectively taken up by HCC cells (e.g. Hep3B, HepG2, and Huh 7). Interestingly, Hep3B cells induced the highest cytotoxicity compared with HepG2 and Huh7 cells, and substantially enhanced the apoptosis by NK-exo. Furthermore, we demonstrated that NK-exo inhibited the phosphorylation of serine/threonine protein kinases (e.g. AKT and ERK1/2), and enhanced the activation of specific apoptosis markers (e.g. caspase-3, -7, -8, -9, and PARP) in Hep3B cells. NK-exo also exhibit the active targeting ability and potent therapeutic effects in both orthotopic and subcutaneous HCC mouse models. Overall, these results suggest that NK-exo indicate strong anti-tumor effects in HCC, which are mediated by novel regulatory mechanisms involved in serine/threonine kinase pathway-associated cell proliferation and caspase activation pathway-associated apoptosis.

MATERIALS
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Brand
Product Description

Sigma-Aldrich
Akt Inhibitor, The Akt Inhibitor controls the biological activity of Akt. This small molecule/inhibitor is primarily used for Phosphorylation & Dephosphorylation applications.
Pricing and availability is not currently available.
Sigma-Aldrich
U0126, U0126, CAS 109511-58-2, is a potent and specific inhibitor of MEK1 (IC₅₀ = 72 nM) and MEK2 (IC₅₀ = 58 nM). The inhibition is noncompetitive with respect to both ATP and ERK.
Pricing and availability is not currently available.