我们从高原芽孢杆菌中纯化了肽酶 M84，以便从环境微生物分离株中分离出抗癌蛋白酶。这种金属蛋白酶对正常细胞存活没有明显影响，但它特异性诱导卵巢癌细胞凋亡。 PAR-1 是一种 GPCR，据报道在卵巢癌细胞中过度表达，被确定为肽酶 M84 的靶标。我们观察到肽酶 M84 诱导 PAR-1 过度表达，并激活其下游信号效应器 NF-κB 和 MAPK，从而促进过量活性氧 (ROS) 的产生。这通过内在途径引起卵巢癌细胞的凋亡。在体内实验中，同系小鼠每周腹腔注射肽酶 M84 可显着减少腹水积聚，使小鼠存活率提高 60%。总的来说，我们的研究结果表明肽酶 M84 触发 PAR-1 介导的氧化应激，充当细胞凋亡诱导剂。这确立了肽酶 M84 作为受体介导的卵巢癌靶向治疗的候选药物。© 2024 作者。

We have purified Peptidase M84 from Bacillus altitudinis in an effort to isolate anticancer proteases from environmental microbial isolates. This metallo-protease had no discernible impact on normal cell survival, but it specifically induced apoptosis in ovarian cancer cells. PAR-1, a GPCR which is reported to be overexpressed in ovarian cancer cells, was identified as a target of Peptidase M84. We observed that Peptidase M84 induced PAR-1 overexpression along with activating its downstream signaling effectors NF-κB and MAPK to promote excessive reactive oxygen species (ROS) generation. This evoked apoptotic death of the ovarian cancer cells through the intrinsic route. In in vivo set-up, weekly intraperitoneal administration of Peptidase M84 in syngeneic mice significantly diminished ascites accumulation, increasing murine survival rates by 60%. Collectively, our findings suggested that Peptidase M84 triggered PAR-1-mediated oxidative stress to act as an apoptosis inducer. This established Peptidase M84 as a drug candidate for receptor mediated targeted-therapy of ovarian cancer.© 2024 The Author(s).