Pinl抑制剂Juglone对食管癌EC1细胞增殖的抑制作用

目的:测定Pinl抑制剂(Juglone)对食管癌细胞EC1生长增殖的影响,探讨Juglone的抗肿瘤作用.方法:体外培养人食管癌细胞系EC1,用MTT试验观察细胞生长增殖状况,流式细胞仪检测细胞周期以及细胞凋亡.结果:MTT试验表明,Juglone对EC1细胞生长有明显的抑制作用,且抑制作用随作用浓度和作用时间增加而增强.流式细胞仪检测表明,加入Juglone培养48h后,EC1细胞出现G2期阻滞.Juglone药物(10、20、30μmol/L)培养48h后,EC1细胞的凋亡率明显增加,与对照组相比有统计学意义(9.06%,32.88%,53.18%vs8.77%,均P<0.05).结论:Pinl抑制剂Juglone可以通过抑制Pinl表达从而抑制食管癌细胞的增殖,Pinl抑制剂有望成为新型的抗肿瘤治疗靶点.

Juglone联合顺铂抑制食管癌EC1细胞增殖的研究

目的研究Pinl抑制剂Juglone与化疗药物顺铂(CDDP)单独及联合使用对食管癌EC1细胞增殖的抑制作用。方法使用不同浓度Juglone、CDDP或者两药联用处理食管癌EC1细胞后,应用MTT法测定两药单独或联合使用对食管癌EC1细胞增殖的影响,使用流式细胞仪检测其对EC1细胞周期的影响。结果 Juglone对EC1细胞的生长有明显的抑制作用,48 h细胞抑制率从11.5%上升到50.7%,具有显著的剂量效应。Juglone可造成食管癌细胞在G2/M+S期的阻滞;CDDP可增加EC1细胞对于Juglone的敏感性,CDDP与Juglone合用,明显提高了EC1细胞的生长抑制率。结论 Juglone与CDDP联合能显著抑制食管癌EC1细胞的增殖。

Pin1抑制剂Juglone对宫颈癌细胞增殖的抑制作用

目的比较Pin1抑制剂(Juglone)和环磷酰胺(CTX)对4株宫颈癌细胞生长的影响,以探讨Juglone的抗肿瘤作用。方法体外培养人宫颈癌细胞系HeLa、SiHa、C33a以及Caski,用细胞生长曲线和MTT试验观察细胞生长状况,流式细胞仪检测细胞周期,Western blot和比色法检测Caspase3蛋白表达及活性。结果细胞生长曲线和MTT试验均表明,Juglone对4株宫颈癌细胞生长有明显的抑制作用,且抑制作用随作用浓度和作用时间增加而增强。流式细胞仪检测表明,Juglone(50μmol/L)培养24h后,G2/M期细胞比例数较CTX组明显增加,而G0/G1期细胞比例数却较CTX组降低。Western blot和比色法显示Juglone各浓度组中Caspase3活性明显高于CTX组。结论Juglone可能通过体外抑制细胞增殖,诱导细胞凋亡等途径抑制肿瘤的发展。

Juglone对人鼻咽癌细胞株CNE-2Z细胞增殖及细胞周期的抑制作用

目的测定Pin1抑制剂(Juglone)对人鼻咽癌细胞株CNE-2Z细胞生长增殖及细胞周期的影响,讨论Ju-glone的抗鼻咽癌肿瘤的作用效果。方法体外培养人鼻咽癌CNE-2Z细胞,采用MTT实验观察细胞生长增殖状况,流式细胞仪检测细胞周期。结果 MTT测定结果显示,Juglone对人鼻咽癌细胞株CNE-2Z细胞生长有明显的抑制作用,并且随着时间的延长和作用浓度的升高,其抑制作用也逐渐增强;流式细胞仪分析检测结果显示,加入Juglone培养24 h后造成CNE-2Z细胞G1期阻滞,48 h后,CNE-2Z细胞G2/M期阻滞(P<0.01)。结论 Juglone有抑制鼻咽癌细胞增殖和细胞周期阻滞的作用,有望为鼻咽癌防治提供候选药物。

Experimental study on the apoptosis of cervical cancer Hela cells induced by juglone through c-Jun N-terminal kinase/c-Jun pathway

Objective: To study the regulatory effect and molecular mechanism of juglone on apoptosis of cervical cancer Hela cells. Methods: Cervical cancer Hela cells were cultured and treated with different dosages of juglone (10, 20, and 40 pmol/L, respectively) and c-Jun N-terminal kinase (JNK) inhibitor SP600125 (10, 20, and 40 mu mol/L. respectively). Then cellular proliferative activity and the expression of JNK/c-Jun pathway molecule and apoptotic molecule in the cells were detected. Results: After 6, 12. 18 and 24 h of treatment, the value for proliferative activity of cells treated with juglone was significantly lower than that of control group (p<0.05), and the anti-proliferative effect was more significant as the treatment period and juglone dosage increased (P<0.05). The protein expressions of Box, CytC, Fas, FasL, Caspase-3, and p-c-Jun in cells treated with juglone were significantly higher than those of control group (P<0.05), and the protein expressions of Bax, CytC, Fas. FasL, Caspase-3, p-JNK and p-c-Jun increased more remarkably as the juglone dosage increased (P<0.05). In cells treated with 40 pmol/L juglone and SP600125, the protein expressions of Bax, CytC, Fas. Fast.. and Caspase-3 were significantly lower than those of cells treated with 40 pmol/L juglone (J<0.05), and the protein expressions of Bax, CytC, Fas, FasL and Caspase-3 reduced more remarkably as the SP600125 dosage increased (P<0.05). Conclusion: Juglone can increase the expression of apoptotic molecules in mitochondrial pathway and death receptor pathway by activating JNK/c-Jun pathway, thus inducing apoptosis of cervical cancer cells.

Effect of Juglone in qinglongyi on cell cycle status and apoptosis in A-549 cells

Objective To explore the inhibition of juglone in Qinglongyi on A-549 cells in vitro.Methods MTT assay was used.Laser confocal scanning microscope was used to observe apoptotic morphology.Changes of cell cycle are studied by flow cytometry analysis.Results MTT assay showed that juglone had a marked growth inhibition in A-549 cells and the IC50 is respectively 3.4×10-5 mol·L-1,1.8×10-5 mol·L-1 and 2.6×10-6 mol·L-1 after treatment for 24,48 and 72 h by juglone.Through Laser confocal scanning microscope,we can see that juglone can induce the apoptosis.Cell cycle changes are analyzed by flow cytometry with cells at G1 phase significantly less than those of control and cells at G2 phase significantly more than those of control.Conclusions It suggests that juglone could apoptosis of A-549 cells with the cell cycle arrest on G2 phase in distinct dose-dependent manner.

Effect of juglone on immunity response and oxidative stress in mice

To research juglone＇s immunology regulation, several perspectives including immunology regulation, lymphocyte proliferation, and cytokines were presented. The index of thymus and spleen, total supperoxide dismutase activity （T-SOD）, serum malondialdehyde （MDA）, content of nitrogen oxide （NO）, the anti-superoxide anion ability, the suppressing hydroxy radical ability, contents of reduced glutathione （GSH） in thymus, total antioxidationabiUty （T-AOC） and the level of mouse ly- sozyme （LZM） in plasma were measured. LPS-induced B thymocytes proliferation was measured by MTT assay. In the low-immunity model group, MDA and NO levels were decreased （p 〈0. 001）. Ju- glone improved lysozyme （LZM）, GSH contents in thymus, T-AOC, T-SOD activity, the anti-super- oxide anion ability （anti- O2-） （p 〈0. 001）. In the stimulation immunity model group, MDA and NO levels （p 〈0. 05）, anti- 02- and T-SOD activity （p 〈0. 05） were up-regulated, whereas LZM, T-AOC contents were down-regulated, juglone has a significant effect, which promotes cell regeneration and function recovery, also may alleviate oxidative damage; juglone possesses a dual regulating effect on humoral immunity in mice.

Fe(Ⅲ)-juglone nanoscale coordination polymers for cascade chemodynamic therapy through synergistic ferroptosis and apoptosis strategy

Chemodynamic therapy(CDT)relying on the transformation of endogenous hydrogen peroxide(H_(2)O_(2))into cytotoxic hydroxyl radicals(·OH)based on the catalysis of Fenton/Fenton-type reactions exhibits great potentiality for cancer treatment.However,the inadequate H_(2)O_(2)supply and intricate redox homeostasis in tumor microenvironment(TME)severely impair the efficacy of CDT.Herein,we design selfassembled 1,2-distearoyl-sn-glycero-3-phosphoethanolamine conjugated polyethylene glycol(DSPE-PEG)-modified Fe(Ⅲ)-juglone nanoscale coordination polymers(FJP NCPs)as redox homeostasis disruptors for juglone-enhanced CDT.Responding to glutathione(GSH)-rich and acidic TME,the Fe^(2+)/Fe^(3+)-guided CDT and GSH consumption by Fe^(3+)are activated,resulting in·OH downstream and up-regulation of lipid peroxidation(LPO).In addition,the released juglone not only depletes GSH through Michael addition,but also elevates intracellular H_(2)O_(2)level for achieving·OH further bursting.With the impressive efficiency of GSH exhaustion and reactive oxygen species(ROS)storm generation,ferroptosis and apoptosis are significantly enhanced by FJP NCPs in vivo.In brief,this facile and efficient design for versatile nanoscale coordination polymers presents a novel paradigm for effectively elevating CDT efficiency and tumor synergistic therapy.

Jug-PLGA-NPs, a New Form of Juglone with Enhanced Efficiency and Reduced Toxicity on Melanoma

Objective: To verrify the anti-tumor efficacy and toxicity between juglone(Jug) and Jug-loaded poly lactic-co-glycolic acid(PLGA) nanoparticles(Jug-PLGA-NPs). Methods: Jug-PLGA-NPs were prepared by ultrasonic emulsification. The anti-tumor activity of Jug(2, 3, 4 μg/mL) and Jug-PLGA-NPs(Jug: 2, 3, 4 μg/mL) in vitro was measured by MTT assay and cell apoptosis analysis. The distribution, anti-tumor effect and biological safety in vivo was evaluated on A375 nude mice. Results: With the advantage of good penetration and targeting properties, Jug-PLGA-NPs significantly inhibited proliferation and migration of melanoma cells both in vitro and in vivo(P<0.05 or P<0.01) with acceptable biocompatibility. Conclusions: Jug can inhibit the growth of melanoma but is highly toxic. With the advantage of sustained release, tumor targeting, anti-tumor activity and acceptable biological safety, Jug-PLGA-NPs provide a new pharmaceutical form for future application of Jug.

Insecticidal activities and active components of the alcohol extract from green peel of Juglans mandshurica

The extract of green peel of Juglans mandshurica Maxim was extracted by common method for studying its insecticidal activities and analyzing the active components. Results showed that the alcohol extract and the chloroform part of extract （separated with chloroform from alcohol extract） form green peel of J. mandshurica have insecticidal activities in contact toxicity and stomach toxicity against larvae of Lymantria dispar L.. After application of the extracts for five days, the corrected mortality of larvae of Lymantria dispar for both extracts was more than 50% in contact toxicity and stomach toxicity at the concentration of ≥ 5 g·L^-1. The insecticidal activity for both alcohol extract and chloroform part of extract is more effect in contact toxicity than in stomach toxicity, but no significant difference in the insecticidal activities was found between alcohol extract and chloroform part of extract. The active components in the chloroform part of extract from green peel of.J. mandshurica were analyzed by GC-MS. The analyzed results showed that the active components in the chloroform part of extract are： （1） joglone （5-hydroxy-1,4- naphthaoquinone）, the relative content 27.11%, （2） 1,5-Naphthalenediol, the relative content 9.52%, （3） 7-Methoxy-1-tetralone, the relative content 6.81%, （4） Benzofuran, 2,3-dihydro-, the relative content 6.76%, （5） 4-Hydroxy-2-methoxycinnamaldehyde, the relative content 3.99%, （6） 2-Methoxy-4-vinylphenol, the relative content 3.05%.

Pin1抑制剂对宫颈癌SiHa细胞增殖和凋亡的影响

目的:研究Pin1抑制剂(Juglone)对宫颈癌SiHa细胞增殖和凋亡的影响,探讨Juglone的抗肿瘤作用。方法:体外培养人宫颈癌细胞SiHa,采用MTT试验观察细胞生长抑制状况,流式细胞仪检测细胞周期阻滞以及Hoechst33258检测细胞凋亡情况。结果:MTT试验表明,Juglone对宫颈癌SiHa细胞生长有明显的抑制作用,且随着作用浓度和作用时间的增加,抑制作用增强。流式细胞仪检测表明,Juglone药物(50μmol/L)培养12、24、48 h后,G2/M期细胞比例数明显增加,而S期细胞比例数却较对照组降低。Hoechst33258实验组可见凋亡细胞。结论:Juglone可能通过体外抑制细胞增殖,诱导细胞凋亡途径抑制宫颈癌的发展。