PDF(Pubmed)
Abstract：
Background: P7C3 is a novel compound that has been widely applied in neurodegenerative diseases and nerve injury repair. Here, we show that higher concentrations of P7C3 than are required for in vivo neuroprotection have the novel function of suppressing renal cell carcinoma (RCC) proliferation and metastasis. Methods: Colony formation, CCK-8 and EdU assay were applied to evaluate RCC cell proliferation. Wound healing and transwell assay were used to measure RCC cell migration and invasion. Flow cytometry assay was employed to detect RCC cell apoptosis and cell cycle. qRT-PCR assay was carried out to measure ribonucleotide reductase subunit M2 (RRM2) mRNA expression level, while western blot assay was utilized to detect the expression level of target proteins. RCC cell growth in vivo was determined by xenografts in mice. Results: We observed that high concentrations of P7C3 could restrain the proliferation and metastasis of RCC cells and promote cell apoptosis. Mechanistically, this new effect of higher dose of P7C3 was associated with reduced expression of RRM2, and the beneficial efficacy of P7C3 in RCC was blocked when suppression of RRM2 was prevented. When RRM2 suppression was permitted, the cGAS-STING pathway was activated by virtue of RRM2/Bcl-2/Bax signaling. Lastly, intraperitoneal injection of this high level of P7C3 in mice potently inhibited tumor growth. Conclusion: In conclusion, we show here that P7C3 that exerts an anti-cancer effect in RCC. Our study indicated that P7C3 might act as a novel drug for RCC in the future. The regulatory signal pathway RRM2/Bcl-2/BAX/cGAS-STING might present novel insight to the potential mechanism of RCC development.
摘要：
背景：P7C3是一种新型化合物，已广泛应用于神经退行性疾病和神经损伤修复。这里,我们表明，P7C3的浓度高于体内神经保护所需的浓度，具有抑制肾细胞癌（RCC）增殖和转移的新功能。方法：集落形成，CCK-8和EdU测定用于评价RCC细胞增殖。使用伤口愈合和transwell测定来测量RCC细胞迁移和侵袭。流式细胞术检测RCC细胞凋亡和细胞周期。qRT-PCR检测核糖核苷酸还原酶亚基M2(RRM2)mRNA表达水平,而蛋白质印迹法用于检测靶蛋白的表达水平。通过小鼠中的异种移植物测定体内RCC细胞生长。结果：我们观察到高浓度的P7C3可以抑制RCC细胞的增殖和转移，并促进细胞凋亡。机械上,较高剂量P7C3的这一新作用与RRM2的表达降低相关,当抑制RRM2时,P7C3在RCC中的有益功效被阻断.当RRM2抑制被允许时,cGAS-STING通路通过RRM2/Bcl-2/Bax信号激活。最后,在小鼠中腹膜内注射这种高水平的P7C3可有效抑制肿瘤生长。结论：总之，我们在这里显示P7C3在RCC中发挥抗癌作用。我们的研究表明，P7C3可能是未来治疗RCC的新药。调控信号通路RRM2/Bcl-2/BAX/cGAS-STING可能为RCC发生发展的潜在机制提供了新的见解。
