CPBMF65 是一种合成的人尿苷磷酸化酶-1 抑制剂，可通过细胞周期停滞和衰老减少 HepG2 细胞增殖。,Investigational New Drugs

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CPBMF65 是一种合成的人尿苷磷酸化酶-1 抑制剂，可通过细胞周期停滞和衰老减少 HepG2 细胞增殖。
Investigational New Drugs ( IF 3.0 ) Pub Date : 2020-05-04 , DOI: 10.1007/s10637-020-00941-2
Elisa Feller Gonçalves da Silva ₁ , Kelly Goulart Lima ₁ , Gabriele Catyana Krause ₁ , Gabriela Viegas Haute ₁ , Leonardo Pedrazza ₁ , Anderson Velasque Catarina ₂ , Rodrigo Benedetti Gassen ₃ , Bruno de Souza Basso ₁ , Henrique Bregolin Dias ₁ , Carolina Luft ₁ , Maria Claudia Rosa Garcia ₁ , Bruna Pasqualotto Costa ₁ , Géssica Luana Antunes ₁ , Luiz Augusto Basso ₄ , Márcio Vinícius Fagundes Donadio ₁ , Pablo Machado ₄ , Jarbas Rodrigues de Oliveira ₁

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肝细胞癌 (HCC) 是原发性肝脏肿瘤中最常见的肿瘤类型，也是全球癌症相关死亡的第二大原因。目前的疗法存在争议，需要更多的研究来确定有效的治疗方法。一种新的合成化合物，钾 5-cyano-4-methyl-6-oxo-1,6-dihydropyridine-2-olate (CPBMF65)，是人尿苷磷酸化酶-1 (hUP1) 酶的有效抑制剂，它控制尿苷 (Urd) 的细胞浓度。Urd 是一种天然嘧啶核苷，参与细胞过程，例如 RNA 合成。此外，它被认为是一种很有前途的生化调节剂，因为它可以降低化疗药物引起的毒性而不损害其抗肿瘤活性。因此，本研究的目的是评估 CPBMF65 对人肝癌细胞系 (HepG2) 增殖的影响。分析了细胞增殖、细胞毒性、细胞凋亡、衰老、自噬、细胞内 Urd 水平、细胞周期停滞和耐药性。结果表明，在与 CPBMF65 孵育后，HepG2 细胞增殖减少，主要是通过细胞周期停滞和衰老，增加细胞内 Urd 的水平并维持慢性治疗期间细胞增殖减少。总之，结果首次显示 hUP1 抑制剂 (CPBMF65) 通过细胞周期停滞和衰老减少 HepG2 细胞增殖的能力。分析细胞周期停滞和耐药性。结果表明，在与 CPBMF65 孵育后，HepG2 细胞增殖减少，主要是通过细胞周期停滞和衰老，增加细胞内 Urd 的水平并维持慢性治疗期间细胞增殖减少。总之，结果首次显示 hUP1 抑制剂 (CPBMF65) 通过细胞周期停滞和衰老减少 HepG2 细胞增殖的能力。分析细胞周期停滞和耐药性。结果表明，在与 CPBMF65 孵育后，HepG2 细胞增殖减少，主要是通过细胞周期停滞和衰老，增加细胞内 Urd 的水平并维持慢性治疗期间细胞增殖减少。总之，结果首次显示 hUP1 抑制剂 (CPBMF65) 通过细胞周期停滞和衰老减少 HepG2 细胞增殖的能力。

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CPBMF65, a synthetic human uridine phosphorylase-1 inhibitor, reduces HepG2 cell proliferation through cell cycle arrest and senescence.

Hepatocellular carcinoma (HCC) is the most prevalent type of tumor among primary liver tumors and is the second highest cause of cancer-related deaths worldwide. Current therapies are controversial, and more research is needed to identify effective treatments. A new synthetic compound, potassium 5-cyano-4-methyl-6-oxo-1,6-dihydropyridine-2-olate (CPBMF65), is a potent inhibitor of the human uridine phosphorylase-1 (hUP1) enzyme, which controls the cell concentration of uridine (Urd). Urd is a natural pyrimidine nucleoside involved in cellular processes, such as RNA synthesis. In addition, it is considered a promising biochemical modulator, as it may reduce the toxicity caused by chemotherapeutics without impairing its anti-tumor activity. Thus, the objective of this study is to evaluate the effects of CPBMF65 on the proliferation of the human hepatocellular carcinoma cell line (HepG2). Cell proliferation, cytotoxicity, apoptosis, senescence, autophagy, intracellular Urd levels, cell cycle arrest, and drug resistance were analyzed. Results demonstrate that, after incubation with CPBMF65, HepG2 cell proliferation decreased, mainly through cell cycle arrest and senescence, increasing the levels of intracellular Urd and maintaining cell proliferation reduced during chronic treatment. In conclusion, results show, for the first time, the ability of a hUP1 inhibitor (CPBMF65) to reduce HepG2 cell proliferation through cell cycle arrest and senescence.

更新日期：2020-05-04

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