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Neferine induces mitochondrial dysfunction to exert anti-proliferative and anti-invasive activities on retinoblastoma.
Experimental Biology and Medicine ( IF 2.8 ) Pub Date : 2020-05-28 , DOI: 10.1177/1535370220928933
Jing Wang 1 , Yanmin Dong 1 , Qiuming Li 1
Affiliation  

Retinoblastoma is common primary intraocular malignancy of infants and childhood. Neferine is a major bisbenzylisoquinoline alkaloid derived from the lotus plumule in Nelumbo nucifera. This study evaluated the mitigation role of Neferine on retinoblastoma in vitro and in vivo. Xenotransplantation model was established by injecting WERI-Rb-1 cells subcutaneously. Upon induction of retinoblastoma , mice were intraperitoneally injected with Neferine (0, 0.5, 1, 2 mg/kg) or ethanol every 3 days for 30 days. Tumor weight and tumor volume were measured every three days and compared between four groups. Then, mice were sacrificed and immunohistochemical examination was performed to compare Ki67, VEGF content between groups. WERI-Rb-1 cells were used for in vitro experiments and the anti-angiogenic role of Neferine was assessed by analyzing nodes/HPF number. In WERI-Rb-1 xenotransplantation model, compared with control group, 1 mg/kg Neferine treatment significantly inhibited tumor weight (0.39 ± 0.04 g vs. 0.25 ± 0.03 g, P< 0.05) and tumor volume (2163 ± 165 mm3 vs. 1276 ± 108 mm3, P< 0.05) after 30 days. Compared with ethanol-injected mice, 2 μM Neferine treatment significantly enhanced apoptosis rate (2.1 ± 0.6% vs. 14.6 ± 2.6%, P< 0.05), accompany downregulation of Ki67 (0.09 ± 0.02% vs. 0.01 ± 0.004%, P< 0.05) and VEGF (0.28 ± 0.04% vs. 0.05 ± 0.03%, P< 0.05) expression. Additionally, 2 μM Neferine treatment significantly decreased JC-1 red/green percentage. High-dose Neferine could decrease retinoblastoma angiogenesis in association with a significant inhibition on tumor growth and invasion. These findings suggested that Neferine could be a new treatment or adjuvant against retinoblastoma.



中文翻译:

Neferine 诱导线粒体功能障碍,对视网膜母细胞瘤发挥抗增殖和抗侵袭活性。

视网膜母细胞瘤是婴儿和儿童常见的原发性眼内恶性肿瘤。Neferine 是一种主要的双苄基异喹啉生物碱,来自Nelumbo nucifera的莲子心。本研究评估了 Neferine在体外体内对视网膜母细胞瘤的缓解作用。通过皮下注射WERI-Rb-1细胞建立异种移植模型。在诱导视网膜母细胞瘤后,每 3 天给小鼠腹膜内注射 Neferine (0, 0.5, 1, 2 mg/kg) 或乙醇,共 30 天。每三天测量一次肿瘤重量和肿瘤体积,并在四组之间进行比较。然后处死小鼠并进行免疫组织化学检查以比较组间Ki67、VEGF含量。WERI-Rb-1 细胞用于体外实验和 Neferine 的抗血管生成作用是通过分析节点/HPF 数来评估的。在 WERI-Rb-1 异种移植模型中,与对照组相比,1 mg/kg Neferine 治疗显着抑制肿瘤重量(0.39 ± 0.04 g vs. 0.25 ± 0.03 g,P < 0.05)和肿瘤体积(2163 ± 165 mm 3 vs . 1276 ± 108 mm 3 , P < 0.05) 30 天后。与注射乙醇的小鼠相比,2 μM Neferine 处理显着提高了细胞凋亡率(2.1 ± 0.6% vs. 14.6 ± 2.6%,P < 0.05),伴随着 Ki67 的下调(0.09 ± 0.02% vs. 0.01 ± 0.004%,P < 0.05)0.05) 和 VEGF (0.28 ± 0.04% vs. 0.05 ± 0.03%, P< 0.05) 表达。此外,2 μM Neferine 处理显着降低了 JC-1 红色/绿色百分比。高剂量 Neferine 可减少视网膜母细胞瘤血管生成,并显着抑制肿瘤生长和侵袭。这些发现表明 Neferine 可能是一种新的治疗方法或辅助治疗视网膜母细胞瘤的方法。

更新日期:2020-05-28
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