N-甲基桑戈啉素（MSSV）是从根癌充血菌（Fusarium solani f. radicicola）中获取的环状五肽内酯类物质。本研究探究了MSSV对结肠直肠癌的抗肿瘤作用。MSSV通过下调CDK 2、CDK6、cyclin D和cyclin E以及上调p21WAF1和p27KIP1来诱导HCT116细胞的G0/G1细胞周期阻滞，从而抑制了细胞的增殖。MSSV处理后发现AKT的磷酸化水平下降。此外，MSSV处理诱导半胱氨酸蛋白酶介导的凋亡，提高了剪切的半胱氨酸蛋白酶3、PARP、半胱氨酸蛋白酶9和促凋亡Bax的水平。MSSV降低了AP-1、Sp-1和NF-κB结合活性所介导的MMP-9水平，从而抑制了HCT116细胞的迁移和侵袭。使用大鼠肝脏S9分离物进行体外代谢测定，检查MSSV代谢物的影响。代谢过程通过降低cyclin D1表达和AKT磷酸化来增强MSSV对HCT116细胞增殖的抑制效果。最后，口服MSSV抑制了HCT116异种移植小鼠的肿瘤生长。这些结果表明，MSSV是结肠直肠癌治疗中一种具有潜力的抗肿瘤剂。版权所有 © 2023 Park、Moon、Lee。

N-methylsansalvamide (MSSV), a cyclic pentadepsipeptide, was obtained from a strain of Fusarium solani f. radicicola. The current study investigated the anti-colorectal cancer effect of MSSV. MSSV exhibited the inhibition of the proliferation in HCT116 cells via induction of G0/G1 cell cycle arrest by downregulating CDK 2, CDK6, cyclin D, and cyclin E, and upregulating p21WAF1 and p27KIP1. Decreased phosphorylation of AKT was observed in MSSV-treated cells. Moreover, MSSV treatment induced caspase-mediated apoptosis through elevating the level of cleaved caspase 3, cleaved PARP, cleaved caspase 9, and pro-apoptotic Bax. MSSV revealed the declined MMP-9 level mediated by reduction in the binding activity of AP-1, Sp-1, and NF-κB motifs, which led to the migration and invasion of HCT116 cells. In vitro metabolism with rat liver S9 fractions was performed to examine the effect of MSSV metabolites. The metabolic process enhanced the inhibitory effect of MSSV on the HCT116 cell proliferation via decline of cyclin D1 expression and AKT phosphorylation. Finally, oral administration of MSSV inhibited the tumor growth of HCT116 xenograft mice. These results suggest that MSSV is a potential anti-tumor agent in colorectal cancer treatment.Copyright © 2023 Park, Moon and Lee.