Neferine induces mitochondrial dysfunction to exert anti-proliferative and anti-invasive activities on retinoblastoma.
Exp Biol Med (Maywood). 2020 May 28:1535370220928933. Epub 2020 May 28. PMID: 32460625
Retinoblastoma is common primary intraocular malignancy of infants and childhood. Neferine is a major bisbenzylisoquinoline alkaloid derived from the lotus plumule in. This study evaluated the mitigation role of Neferine on retinoblastomaand. 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 forexperiments 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,< 0.05) and tumor volume (2163 ± 165 mmvs. 1276 ± 108 mm,< 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%,< 0.05), accompany downregulation of Ki67 (0.09 ± 0.02% vs. 0.01 ± 0.004%,< 0.05) and VEGF (0.28 ± 0.04% vs. 0.05 ± 0.03%,< 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 anew treatment or adjuvant against retinoblastoma.