Laboratory of Molecular Biology and Viral Oncogenesis, National Cancer Institute G Pascale, Naples, Italy.
Int J Nanomedicine. 2012;7:5683-91. doi: 10.2147/IJN.S34723. Epub 2012 Nov 9.
Epidemiological, clinical, and laboratory studies have suggested that ibuprofen, a commonly used nonsteroidal anti-inflammatory drug, inhibits the promotion and proliferation of certain tumors. Recently, we demonstrated the antiproliferative effects of ibuprofen on the human gastric cancer cell line MKN-45. However, high doses of ibuprofen were required to elicit these antiproliferative effects in vitro. The present research compared the antiproliferative effects of ibuprofen delivered freely and released by poly(lactic-co-glycolic acid) (PLGA) nanoparticles (NPs) in MKN-45 cells.
MKN-45 human gastric adenocarcinoma cells were treated with ibuprofen-loaded PLGA NPs. The proliferation of MKN-45 cells was then assessed by cell counting. The uptake of NPs was imaged by fluorescence microscopy and flow cytometry. The release of ibuprofen from ibuprofen-loaded PLGA NPs in the cells was evaluated by gas chromatography-mass spectrometry.
Dramatic inhibition of cellular proliferation was observed in cells treated with ibuprofen-loaded PLGA NPs versus those treated with free ibuprofen at the same concentration. The localization of NPs was cytoplasmic. The initiation of ibuprofen release was rapid, commencing within 2 hours, and then increased slowly over time, reaching a maximum concentration at 24 hours. The inhibition of proliferation was confirmed to be due to the intracellular release of ibuprofen from the NPs. Using PLGA NPs as carriers, ibuprofen exerted an antiproliferative activity at concentrations > 100 times less than free ibuprofen, suggesting greater efficiency and less cellular toxicity. In addition, when carried by PLGA NPs, ibuprofen more quickly induced the expression of transcripts involved in proliferation and invasiveness processes.
Ibuprofen exerted an antiproliferative effect on MKN-45 cells at low concentrations. This effect was achieved using PLGA NPs as carriers of low doses of ibuprofen.
流行病学、临床和实验室研究表明，布洛芬是一种常用的非甾体抗炎药，可抑制某些肿瘤的促进和增殖。最近，我们证明了布洛芬对人胃癌细胞系 MKN-45 的增殖抑制作用。然而，体外需要高剂量的布洛芬才能产生这些增殖抑制作用。本研究比较了自由给予和聚（乳酸-共-乙醇酸）（PLGA）纳米粒子（NPs）释放的布洛芬对 MKN-45 细胞的增殖抑制作用。
用载有布洛芬的 PLGA NPs 处理 MKN-45 人胃腺癌细胞。然后通过细胞计数评估 MKN-45 细胞的增殖。通过荧光显微镜和流式细胞术对 NPs 的摄取进行成像。通过气相色谱-质谱法评估细胞内布洛芬从载有布洛芬的 PLGA NPs 中的释放。
与相同浓度的自由布洛芬相比，用载有布洛芬的 PLGA NPs 处理的细胞中观察到细胞增殖明显抑制。NPs 的定位在细胞质中。布洛芬的释放起始迅速，在 2 小时内开始，然后随时间缓慢增加，在 24 小时达到最大浓度。增殖抑制被确认为由于 NPs 内的布洛芬释放。使用 PLGA NPs 作为载体，布洛芬在浓度大于自由布洛芬 100 倍的情况下发挥增殖抑制活性，表明效率更高，细胞毒性更小。此外，当用 PLGA NPs 携带时，布洛芬更快地诱导参与增殖和侵袭过程的转录物的表达。
布洛芬在低浓度下对 MKN-45 细胞发挥增殖抑制作用。这种作用是通过使用 PLGA NPs 作为低剂量布洛芬的载体来实现的。
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