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载铋亲脂性纳米粒子(BisBAL NP)抑制小鼠黑素瘤模型中肿瘤细胞的生长。

Bismuth Lipophilic Nanoparticles (BisBAL NP) Inhibit the Growth of Tumor Cells in a Mouse Melanoma Model.

机构信息

Subdirección de Investigación Básica, Instituto Nacional de Cancerología, Ciudad de México, México.

Laboratorio de Biología Molecular, Facultad de Odontología, Universidad Autónoma de Nuevo León, UANL, Monterrey, Nuevo León, México.

出版信息

Anticancer Agents Med Chem. 2022;22(14):2548-2557. doi: 10.2174/1871520622666220215124434.

Abstract

AIM

The objective of this study was to analyze the antitumor effect of BisBAL NP in a mouse melanoma model.

MATERIALS AND METHODS

The antitumor activity of BisBAL NP on murine B16-F10 melanoma cells was determined both in vitro (PrestoBlue cell viability assay and Live/Dead fluorescence) and in vivo, in a mouse model, with the following 15-day treatments: BisBAL NP, negative control (PBS), and cell-death control (docetaxel; DTX). Mouse survival and weight, as well as the tumor volume, were recorded daily during the in vivo study.

RESULTS

BisBAL NP were homogeneous in size (mean diameter, 14.7 nm) and bismuth content. In vitro, 0.1 mg/mL BisBAL NP inhibited B16-F10 cell growth stronger (88%) than 0.1 mg/mL DTX (82%) (*p<0.0001). In vivo, tumors in mice treated with BisBAL NP (50 mg/kg/day) or DTX (10 mg/kg/day) were 76% and 85% smaller than the tumors of negative control mice (*p<0.0001). The average weight of mice was 18.1 g and no statistically significant difference was detected among groups during the study. Alopecia was only observed in all DTX-treated mice. The survival rate was 100% for the control and BisBAL NP groups, but one DTX- treated mouse died at the end of the treatment period. The histopathological analysis revealed that exposure to BisBAL NP was cytotoxic for tumor tissue only, without affecting the liver or kidney.

CONCLUSION

BisBAL NP decreased the tumor growing in a mouse melanoma model without secondary effects, constituting an innovative low-cost alternative to treat melanoma.

摘要

目的

本研究旨在分析 BisBAL NP 在小鼠黑色素瘤模型中的抗肿瘤作用。

材料和方法

采用 PrestoBlue 细胞活力检测法和 Live/Dead 荧光法,在体外评估了 BisBAL NP 对小鼠 B16-F10 黑素瘤细胞的抗肿瘤活性,并在小鼠模型中进行了体内研究,为期 15 天的治疗方案如下:BisBAL NP、阴性对照(PBS)和细胞死亡对照(多西紫杉醇;DTX)。在体内研究期间,每天记录小鼠的存活和体重以及肿瘤体积。

结果

BisBAL NP 粒径均匀(平均直径 14.7nm)且铋含量一致。体外实验中,0.1mg/mL BisBAL NP 对 B16-F10 细胞生长的抑制作用强于 0.1mg/mL DTX(88% vs. 82%,*p<0.0001)。体内实验中,BisBAL NP(50mg/kg/天)或 DTX(10mg/kg/天)治疗的小鼠肿瘤比阴性对照组小鼠的肿瘤小 76%和 85%(*p<0.0001)。在研究期间,各组小鼠的平均体重为 18.1g,组间无统计学差异。脱发仅见于所有 DTX 治疗组的小鼠。对照组和 BisBAL NP 组的存活率为 100%,但一只 DTX 治疗组的小鼠在治疗结束时死亡。组织病理学分析显示,BisBAL NP 暴露仅对肿瘤组织具有细胞毒性,而对肝脏或肾脏没有影响。

结论

BisBAL NP 可抑制小鼠黑色素瘤模型中的肿瘤生长,且无副作用,为治疗黑色素瘤提供了一种创新的低成本替代方案。

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