In Vivo Antitumor Effects of MK615 Led by PD-L1 Downregulation

• Published in: Integrative cancer therapies Vol. 17; no. 3; pp. 646 - 653
• Main Authors: Yanaki, Masashi, Kobayashi, Masayuki, Aruga, Atsushi, Nomura, Minoru, Ozaki, Makoto
• Format: Journal Article
• Language: English
• Published: Los Angeles, CA SAGE Publications 01.09.2018; SAGE PUBLICATIONS, INC; SAGE Publishing
• Subjects: Animals; Antifungal agents; Antineoplastic Agents - pharmacology; Antitumor activity; Apoptosis; B7-H1 Antigen - metabolism; Cell death; Cell Line, Tumor; Cell surface; Down-Regulation - drug effects; Heterografts - drug effects; Inflammation; Ligands; Lymphocytes; Lymphocytes T; Male; Melanoma; Melanoma, Experimental - drug therapy; Metastases; Mice; Mice, Inbred BALB C; Mice, Inbred C57BL; Mice, Nude; NF-kappa B - metabolism; NF-κB protein; PD-1 protein; PD-L1 protein; Plant Extracts - pharmacology; Prunus - chemistry; Prunus mume; Tumor cells; Xenografts; triterpenoid; PD-L1; NF-κB; MK615; mume
• ISSN: 1534-7354; 1552-695X
• DOI: 10.1177/1534735418766403

Background/Aim: MK615 extracted from Prunus mume was reported to have anti-inflammatory effects. In this article, we examined the in vivo antitumor effect of MK615 (an extract from Japanese apricot) using mouse tumor xenografts and focusing on the downregulation of PD-L1 (programmed death-ligand 1), a ligand of programmed cell death-1, a surface protein of activated T cells. Materials and Methods: B16/BL6 melanoma cells were injected into C57BL/6 or BALB/c-nu/nu mice to establish lung metastasis. BALB/c-nu/nu mice (nude mice) were used as a T cell–deficient model. The mice were given MK615 or saline orally every other day for approximately 8 weeks, and their survival was observed. NF-κB (nuclear factor-κB) and PD-L1 expressions of metastatic lung tissues were also examined. Results: The survival rate was improved only in the MK615-treated C57BL/6 mice (P < .05), not in the saline-given control mice or BALB/c-nu/nu mice. The downregulations of NF-κB and PD-L1 were observed in both MK615-treated C57BL/6 and BALB/c-nu/nu mice. These results suggest that the antitumor effects of MK615 are associated with T cell–mediated immunity activated by MK-615-induced PD-L1 downregulation in tumor cells. Conclusion: MK615 is beneficial for a prolonged host survival time in the B16/BL6 melanoma xenograft model associated with T cell–mediated antitumor immunity.