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聚乳酸-羟基乙酸共聚物纳米颗粒递送系统对5-氟尿嘧啶和姜黄素治疗鳞状细胞癌的比较评价

Comparative evaluation of PLGA nanoparticle delivery system for 5-fluorouracil and curcumin on squamous cell carcinoma.

作者信息

Masloub Shaimaa M, Elmalahy Mohamed H, Sabry Dina, Mohamed Wael S, Ahmed Sahar H

机构信息

Oral Pathology Department, Faculty of Dentistry, Ain Shams University, Cairo, Egypt.

Medical Biochemistry and Molecular Biology, Faculty of Medicine, Cairo University, Cairo, Egypt.

出版信息

Arch Oral Biol. 2016 Apr;64:1-10. doi: 10.1016/j.archoralbio.2015.12.003. Epub 2015 Dec 21.

DOI:10.1016/j.archoralbio.2015.12.003
PMID:26735343
Abstract

PURPOSE

The purpose of this study is to assess the effect of 5-fluorouracil nanoparticles and curcumin naoparticles on cell proliferation and the expression of the apoptotic marker (caspase 3) in squamous cell carcinoma cell line.

MATERIAL AND METHODS

PLGA 5-fluorouracil nanopartciles and PLGA curcumin nanoparticles were prepared and applied for 24 and 48h on human laryngeal squamous carcinoma cell line (Hep-2) as regard IC 50 concentration. MTT assay was used for evaluation of cytotoxicity of prepared nanoparticles. Quantitaive reverse transcriptase polymerase chain reaction (QRT-PCR) was used for the assessment of caspase-3 expression in the treated cell line.

RESULTS

The drug release rate profiles was dependent upon polymer to drug ratio, noting that the higher PLGA polymer ratio to 5-fluprouracil or curcumin drug showed faster release rates. On the other hand, the least PLGA polymer ratio to 5-fluprouracil or curcumin drug showed the slowest release rates. MTT assay revelaed that 5-fluorouracil nanoparticels or curcumin nanoparticels showed a clear cytotoxic effect on Hep-2 cell line compared to non treated cancer cells. The RT-PCR assessment of caspase-3 expression revealed that there was a significant increase in caspase-3 expression in Hep-2 cell line treated with 5-fluorouracil nanoparticles or curcumin compared to non treated cancer cells.

CONCLUSION

Curcumin nanoparticles could be more active in inducing apoptosis in short term assays (24h) than long term assays (48h) due to differential cellular uptake. While 5-fluorouracil nanoparticles induced higher significant apoptosis in long term (48h) compared to curcumin group.

摘要

目的

本研究旨在评估5-氟尿嘧啶纳米颗粒和姜黄素纳米颗粒对鳞状细胞癌细胞系中细胞增殖及凋亡标志物(半胱天冬酶3)表达的影响。

材料与方法

制备聚乳酸-羟基乙酸共聚物(PLGA)5-氟尿嘧啶纳米颗粒和PLGA姜黄素纳米颗粒,并以IC50浓度作用于人喉鳞状癌细胞系(Hep-2)24小时和48小时。采用MTT法评估所制备纳米颗粒的细胞毒性。运用定量逆转录聚合酶链反应(QRT-PCR)评估处理后细胞系中半胱天冬酶-3的表达。

结果

药物释放速率曲线取决于聚合物与药物的比例,注意到PLGA聚合物与5-氟尿嘧啶或姜黄素药物的比例越高,释放速率越快。另一方面,PLGA聚合物与5-氟尿嘧啶或姜黄素药物的比例越低,释放速率越慢。MTT分析表明,与未处理的癌细胞相比,5-氟尿嘧啶纳米颗粒或姜黄素纳米颗粒对Hep-2细胞系具有明显的细胞毒性作用。半胱天冬酶-3表达的RT-PCR评估显示,与未处理的癌细胞相比,用5-氟尿嘧啶纳米颗粒或姜黄素处理的Hep-2细胞系中半胱天冬酶-3的表达有显著增加。

结论

由于细胞摄取差异,姜黄素纳米颗粒在短期试验(24小时)中诱导凋亡可能比长期试验(48小时)更具活性。而与姜黄素组相比,5-氟尿嘧啶纳米颗粒在长期(48小时)诱导更高的显著凋亡。

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