Pancreatic ductal adenocarcinoma (PDAC) is a highly lethal disease, and novel therapeutic strategies are urgently needed. Recently, expression of the C-C chemokine receptor 5 (CCR5) and its ligands has been found to play an important role in cancer progression and metastasis. In this study, we blocked the CCR5 receptor by the FDA approved antagonist maraviroc (MVC) in Suit2-007 and MIA-PaCa-2 human PDAC cells. The treatment significantly inhibited their proliferation and induced apoptosis of exposed cells as evidenced by caspases activation and increased Bax levels. Moreover, MVC inhibited the cell cycle by down regulating the proteins of the complexes of cyclin dependent kinase (CDK) 4/6 - Cyclin D and CDK2 - Cyclin E, as well as by increasing the protein levels of CDK inhibitors p18, p21 and p27. In line with this, MVC caused significant retardation of Suit2-007 cells growing in a PDAC liver metastasis xenograft model (p < 0.05). These results suggest that maraviroc could be a promising treatment strategy for PDAC patients with liver metastases.

中文翻译：

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CCR5拮抗剂maraviroc基于细胞周期抑制和凋亡诱导作用，可导致裸鼠胰腺癌肝转移的缓解。

胰腺导管腺癌（PDAC）是一种高度致死性疾病，迫切需要新的治疗策略。最近，已发现CC趋化因子受体5（CCR5）及其配体的表达在癌症进展和转移中起重要作用。在这项研究中，我们在Suit2-007和MIA-PaCa-2人PDAC细胞中被FDA批准的拮抗剂maraviroc（MVC）阻断了CCR5受体。该治疗显着抑制了它们的增殖并诱导了暴露细胞的凋亡，这由胱天蛋白酶激活和Bax水平升高证明。此外，MVC通过下调细胞周期蛋白依赖性激酶（CDK）4/6-细胞周期蛋白D和CDK2-细胞周期蛋白E的复合物的蛋白质，以及通过增加CDK抑制剂p18，p21和p27的蛋白质水平来抑制细胞周期。为此，MVC导致在PDAC肝转移异种移植模型中生长的Suit2-007细胞显着阻滞（p <0.05）。这些结果表明，maraviroc可能是PDAC肝转移患者的有前途的治疗策略。