PLGA载姜黄素纳米粒对人宫颈癌Hela细胞的抑制作用及机制探究
摘要
目的：1.制备聚乳酸-羟基乙酸载姜黄素纳米粒(Cur-PLGA-NPs),观察Cur-PLGA-NPs对人宫颈癌Hela细胞株增殖的抑制作用。2.初步探讨Cur-PLGA-NPs对Hela细胞抑制作用的机制。
方法：1.采用优化的乳液-溶剂挥发法制备Cur-PLGA-NPs,透射电镜下观察纳米粒子形态,紫外可见光分光光度法测定Cur-PLGA-NPs的载药量。2.外培养人宫颈癌细胞株Hela细胞,MTT法测定不同浓度Cur-PLGA-NPs干预对人宫颈癌Hela细胞株的抑制率,流式细胞仪检测细胞凋亡率及周期分布。3.不同浓度Cur-PLGA-NPs干预Hela细胞,荧光定量PCR法检测HPV18E6、 E7RNA含量,Western blot法检测HPV18E6、E7蛋白的表达。
结果：1.成功制备了Cur-PLGA-NPs,粒径主要分布于30nm～150nm,载药量4.6%。2.6.25μmol·L-1、12.5μmol·L-1、25μmol·L-1、50μmol·L-1的Cur-PLGA-NPs可显著抑制Hela细胞生长且诱导细胞凋亡(P<0.01),抑制作用具有时间和浓度依赖性；相同浓度的Cur-PLGA-NPs对Hela细胞生长的抑制作用强于游离姜黄素(P<0.01);50μmol·L-1的Cur-PLGA-NPs使Hela细胞发生明显的G1期阻滞(P<0.01)。3.不同浓度Cur-PLGA-NPs干预Hela细胞后,HPV18E6、E7RNA减少(P<0.05),减少程度与Cur-PLGA-NPs浓度正相关。4.不同浓度Cur-PLGA-NPs干预Hela细胞后,HPV18E6、E7蛋白的表达受到抑制(P<0.05),抑制程度和Cur-PLGA-NPs浓度正相关。
结论：1.优化的乳液-溶剂挥发法可成功制出备性状良好的Cur-PLGA-NPs, Cur-PLGA-NPs可显著抑制Hela细胞的增殖。2.Cur-PLGA-NPs抑制Hela细胞作用的机制是通过下调E6、E7RNA及抑制E6、E7的蛋白的表达来实现的。
OBJECTIVE:1.To prepare curcumin-loaded PLGA nanoparticles (Cur-PLGA-NPs) and to investigate the inhibition effects of Cur-PALG-NPs on the proliferation of Hela cells.2.Preliminary study the mechanism of the inhibition effects.
METHODS:1.Cur-PLGA-NPs were Synthesized by modified emulsion-solvent method. The particle size and morphology were validated under transmission electron microscopy. The drug loading was detected by the UV-vis spectrophotometry.2.Cultivating human cervical carcinoma Hela cells in vitro, the inhibition effects of Cur-PLGA-NPs on Hela cells were observed with MTT assay. The apoptosis rate and the distribution of cell cycle were detected by FCM respectively.3.Intervening Hela cells with different concentration of Cur-PLGA-NPs, the differences of HPV18E6, E7RNA content in cells due to effects of Cur-PLGA-NPs were detected by fluorescence quantitative PCR and the the differences of E6, E7proteins expression by western blot method.
RESULTS:1.The preraration of Cur-PLGA-NPs was successful and the sizes of spherical nanoparticles were mainly distributed in the30nm-150nm range. The drug loading was4.6%.2.6.25μumol·L-1、12.5μmol·L-1、25umol·L-1、50μmol·L-1Cur-PLGA-NPs inhibited the proliferation of Hela cells significantly(P<0.01), with dose and time dependent, and resulted in cell apoptosis(P<0.01). In the same concentration, Cur-PLGA-NPs played stronger role of the inhibition effects than curcumin(P<0.01).50μmol·L-1Cur-PLGA-NPs arrested the cells in G1phase obviously(P<0.01).3. After intervening of Cur-PLGA-NPs in different concentrations, the HPV18E6, E7RNA decreased(P<0.05), and the decreasing sevenrity was related with drug concentration.4.After intervening of different concentrations of Cur-PLGA-NPs, the inhibition effects on E6, E7protein expression were related with drug concentrations(P<0.05).
CONCLUSION:1.Cur-PLGA-NPs with superior traits were synthesized with optimal emulsion-solvent preparition method, and inhibited the proliferation of Hela cells significantly.2.The inhibition mechanism of Cur-PLGA-NPs may be down-regulation of the HPV18E6, E7RNA and the inhibition of the E6, E7proteins expression.
方法：1.采用优化的乳液-溶剂挥发法制备Cur-PLGA-NPs,透射电镜下观察纳米粒子形态,紫外可见光分光光度法测定Cur-PLGA-NPs的载药量。2.外培养人宫颈癌细胞株Hela细胞,MTT法测定不同浓度Cur-PLGA-NPs干预对人宫颈癌Hela细胞株的抑制率,流式细胞仪检测细胞凋亡率及周期分布。3.不同浓度Cur-PLGA-NPs干预Hela细胞,荧光定量PCR法检测HPV18E6、 E7RNA含量,Western blot法检测HPV18E6、E7蛋白的表达。
结果：1.成功制备了Cur-PLGA-NPs,粒径主要分布于30nm～150nm,载药量4.6%。2.6.25μmol·L-1、12.5μmol·L-1、25μmol·L-1、50μmol·L-1的Cur-PLGA-NPs可显著抑制Hela细胞生长且诱导细胞凋亡(P<0.01),抑制作用具有时间和浓度依赖性；相同浓度的Cur-PLGA-NPs对Hela细胞生长的抑制作用强于游离姜黄素(P<0.01);50μmol·L-1的Cur-PLGA-NPs使Hela细胞发生明显的G1期阻滞(P<0.01)。3.不同浓度Cur-PLGA-NPs干预Hela细胞后,HPV18E6、E7RNA减少(P<0.05),减少程度与Cur-PLGA-NPs浓度正相关。4.不同浓度Cur-PLGA-NPs干预Hela细胞后,HPV18E6、E7蛋白的表达受到抑制(P<0.05),抑制程度和Cur-PLGA-NPs浓度正相关。
结论：1.优化的乳液-溶剂挥发法可成功制出备性状良好的Cur-PLGA-NPs, Cur-PLGA-NPs可显著抑制Hela细胞的增殖。2.Cur-PLGA-NPs抑制Hela细胞作用的机制是通过下调E6、E7RNA及抑制E6、E7的蛋白的表达来实现的。
OBJECTIVE:1.To prepare curcumin-loaded PLGA nanoparticles (Cur-PLGA-NPs) and to investigate the inhibition effects of Cur-PALG-NPs on the proliferation of Hela cells.2.Preliminary study the mechanism of the inhibition effects.
METHODS:1.Cur-PLGA-NPs were Synthesized by modified emulsion-solvent method. The particle size and morphology were validated under transmission electron microscopy. The drug loading was detected by the UV-vis spectrophotometry.2.Cultivating human cervical carcinoma Hela cells in vitro, the inhibition effects of Cur-PLGA-NPs on Hela cells were observed with MTT assay. The apoptosis rate and the distribution of cell cycle were detected by FCM respectively.3.Intervening Hela cells with different concentration of Cur-PLGA-NPs, the differences of HPV18E6, E7RNA content in cells due to effects of Cur-PLGA-NPs were detected by fluorescence quantitative PCR and the the differences of E6, E7proteins expression by western blot method.
RESULTS:1.The preraration of Cur-PLGA-NPs was successful and the sizes of spherical nanoparticles were mainly distributed in the30nm-150nm range. The drug loading was4.6%.2.6.25μumol·L-1、12.5μmol·L-1、25umol·L-1、50μmol·L-1Cur-PLGA-NPs inhibited the proliferation of Hela cells significantly(P<0.01), with dose and time dependent, and resulted in cell apoptosis(P<0.01). In the same concentration, Cur-PLGA-NPs played stronger role of the inhibition effects than curcumin(P<0.01).50μmol·L-1Cur-PLGA-NPs arrested the cells in G1phase obviously(P<0.01).3. After intervening of Cur-PLGA-NPs in different concentrations, the HPV18E6, E7RNA decreased(P<0.05), and the decreasing sevenrity was related with drug concentration.4.After intervening of different concentrations of Cur-PLGA-NPs, the inhibition effects on E6, E7protein expression were related with drug concentrations(P<0.05).
CONCLUSION:1.Cur-PLGA-NPs with superior traits were synthesized with optimal emulsion-solvent preparition method, and inhibited the proliferation of Hela cells significantly.2.The inhibition mechanism of Cur-PLGA-NPs may be down-regulation of the HPV18E6, E7RNA and the inhibition of the E6, E7proteins expression.
引文
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