ANTI-CANCER DRUGS
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2021
·Vol. 32
·期 7
·727
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IF 2.248
Zhang Zuo-yan,Dong Shu-min,Liu Ye-han,Zhang Man-man,Zhang Jian-kang,Zhu Hua-jian,Shao Jia-an,Liu Hua-qing,Li Yang-ling,Zhang Chong,Zeng Ling-hui
Vinpocetine is widely used to treat cerebrovascular diseases. However, the effect of vinpocetine to treat hepatocellular carcinoma (HCC) has not been investigated. In this study, we revealed that vinpocetine was associated with antiproliferative activity in HCC cells, but induced cytoprotective autophagy, which restricted its antitumor activity. Autophagy inhibitors improved the antiproliferative activity of vinpocetine in HCC cells. Sorafenib is effective to treat advanced HCC, but the effect of autophagy induced by sorafenib is indistinct. We demonstrated vinpocetine plus sorafenib suppressed the cytoprotective autophagy activated by vinpocetine in HCC cells and significantly induced apoptosis and suppressed cell proliferation in HCC cells. In addition, vinpocetine plus sorafenib activates glycogen synthase kinase 3β (GSK-3β) and subsequently inhibits cytoprotective autophagy induced by vinpocetine in HCC cells. Meanwhile, overexpression of GSK-3β was efficient to increase the apoptosis induced by vinpocetine plus sorafenib in HCC cells. Our study revealed that vinpocetine plus sorafenib could suppress the cytoprotective autophagy induced by vinpocetine and subsequently show synergistically anti-HCC activity via activating GSK-3β and the combination of vinpocetine and sorafenib might reverse sorafenib resistance via the PI3K/protein kinase B/GSK-3β signaling axis. Thus, vinpocetine may be a potential candidate for sorafenib sensitization and HCC treatment, and our results may help to elucidate more effective therapeutic options for HCC patients with sorafenib resistance.
研究领域:
肿瘤学
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药理学
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分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
DRUG DEVELOPMENT AND INDUSTRIAL PHARMACY
·
2019
·
IF 2.367
Jieqiong Lv,Runcheng Liang,Zihua Xia,Yong Li,Zhufen Lv,Dongzhi Hou,Liping Yu,Gang Chen,Yi Liu,Fan Yang
Purpose: A series of β-CD amphiphilic star-shaped copolymers with exceptional characteristics were synthesized and their potential as carriers for micelles drug delivery was investigated.Methods: A series of amphiphilic copolymers based on β-CD were synthesized by introducing poly (acrylic acid)-co-poly(methyl methacrylate)-poly (vinyl pyrrolidone) or poly (acrylic acid)-co-poly(methyl methacrylate)-co-poly(monoacylated-β-CD)-poly (vinyl pyrrolidone) blocks to the primary hydroxyl group positions of β-CD. The micellization behavior of the copolymers, the synthesis conditions, characteristics, drug release in vitro and tissue distribution of vinpocetine (VP) micelles in vivo were investigated.Results: Around 60 types of β-CD amphiphilic star-shaped copolymers were successfully synthesized and the critical micelle concentration ranged from 9.80 × 10−4 to 5.24 × 10−2g/L. The particle size, drug loading and entrapment efficiency of VP-loaded β-CD-P4 micelles prepared with optimal formulation were about 65 nm, 21.44 ± 0.14%, and 49.05 ± 0.36%, respectively. The particles had good sphericity. The cumulative release rates at 72 h of VP-loaded β-CD-P4 micelles in pH 1.0, pH 4.5, pH 6.5, or pH 7.4 media were 93%, 69%, 49%, and 43%, respectively. And, the lung targeting efficiency of VP-loaded β-CD-P4 micelles was 8.98 times higher than that of VP injection.Conclusion: The VP-loaded β-CD-P4 micelles exhibited controlled-release property, pH-induced feature and lung targeting capacity compared with VP injection, suggesting that the β-CD-P4 copolymers are an excellent candidate for micelles drug delivery.
研究领域:
药剂学
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生物材料
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药物化学
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF CHROMATOGRAPHY B-ANALYTICAL TECHNOLOGIES IN THE BIOMEDICAL AND LIFE SCIENCES
·
2015
·
IF 2.729
Zhi Liu,Hai-Long Wu,Yong Li,Hui-Wen Gu,Xiao-Li Yin,Li-Xia Xie,Ru-Qin Yu
A novel chemometrics-assisted high performance liquid chromatography method coupled with diode array detector (HPLC–DAD) was proposed for the simultaneous determination of vincristine (VCR), vinblastine (VLB), vindoline (VDL), catharanthine (CAT) and yohimbine (YHB) in Catharanthus roseus ( C. roseus ) and human serum samples. With the second-order advantage of the alternating trilinear decomposition (ATLD) method, the resolution and rapid determination of five components of interest in complex matrices were performed, even in the present of heavy overlaps and unknown interferences. Therefore, multi-step purification was omitted and five components could be fast eluted out within 7.5 min under simple isocratic elution condition (acetonitrile/0.2% formic acid water, 37:63, v/v). Statistical parameters, such as the linear correlation coefficient ( R 2 ), root-mean-square error of prediction (RMSEP), limit of detection (LOD) and limit of quantitation (LOQ) had been calculated to investigate the accuracy and reliability of the method. The average recoveries of five vinca alkaloids ranged from 97.1% to 101.9% and 98.8% to 103.0% in C. roseus and human serum samples, respectively. The five vinca alkaloids were adequately determined with limits of detection (LODs) of 29.5–49.3 ng mL −1 in C. roseus and 12.4–27.2 ng mL −1 in human serum samples, respectively. The obtained results demonstrated that the analytical strategy provided a feasible alternative for synchronously monitoring the quality of raw herb and the concentration of blood drugs.
研究领域:
植物化学
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药物分析
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分析化学
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产品关联
DOI
PubMed
高影响因子
MOLECULAR PHARMACEUTICS
·
2019
·
IF 4.396
Yongyan Zhu,Ruixuan Liu,Haoji Huang,Quanhong Zhu
Molecularly imprinted polymers have exhibited good performance as carriers on drug loading and sustained release. In this paper, vinblastine (VBL)-loaded polymeric nanoparticles (VBL–NPs) were prepared by a one-step molecular imprinting process, avoiding the waste and incomplete removal of the template, and evaluated as targeting carriers for VBL delivery after modification. Using acryloyl amino acid comonomers and disulfide cross-linkers, VBL–NPs were synthesized and then conjugated with poly(ethylene glycol)–folate. The dynamic size of the obtained VBL–NPs–PEG–FA was 258.3 nm (PDI = 0.250), and the encapsulation efficiency was 45.82 ± 1.45%. The nanoparticles of VBL–NPs–PEG–FA were able to completely release VBL during 48 h under a mimic tumor intracellular condition (pH 4.5, 10 mM glutathione (GSH)), displaying significant redox responsiveness, whereas the release rates were much slower in the mimic body liquid (pH 7.4, 2 μM GSH) and tumor extracellular environment (pH 6.5, 2 μM GSH). Furthermore, the carriers NPs–PEG–FA, prepared without VBL, showed satisfactory intrinsic hemocompatibility, cellular compatibility, and tumor-targeting properties: they could rapidly and efficiently accumulate to folate receptor positive Hela cells and then internalized via receptor-mediated endocytosis, and the retention in tumor tissues could last for over 48 h. Interestingly, VBL–NPs–PEG–FA could evidently increase the accumulation of VBL in tumor tissues while decreasing the distribution of VBL in organs, exert similar anticancer efficacy against Hela tumors in the xenograft model of nude mice to VBL injection, and significantly improve the abnormality of liver and spleen observed in VBL injection. VBL–NPs–PEG–FA has the potential to be the delivery carrier for VBL by enhancing the tumor-targeting efficacy of VBL and decreasing toxicity to normal tissues.
研究领域:
药学
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生物技术
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纳米技术
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癌症研究
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药物递送系统
✓ 已验证
产品关联
DOI
PubMed
高影响因子
PLANT CELL TISSUE AND ORGAN CULTURE
·
2025
·Vol. 162
·期 3
·1-12
·
IF 2.4
Li Haihua,Li Jiahe,Liu Ningjin,Li Huishan,Wang Jiarui,Zhang Rulan,Xue Jingyan,Kang Xiaotian,Guan Xinying,Lin Shiya,Zhang Ziyu,Kuang Jiaqi,Qian Chenlei,Zhou Pengfei
In Catharanthus roseus , the inherently low yield of bioactive alkaloids such as vindoline, catharanthine, ajmalicine, and vinblastine remains a major limitation to their broader therapeutic application, particularly in anticancer and antihypertensive treatments. To address this challenge, we developed a novel metabolic flux regulation strategy by combining the enzyme inhibitors lovastatin and naproxen with the abiotic elicitor copper(II)-chitosan (Cu-CS) complex. Compared to controls, treatment with 2 mg/L lovastatin significantly enhanced catharanthine, vindoline, ajmalicine, and vinblastine accumulation in C. roseus CMCs to 2.38, 0.63, 35.3, and 2.33 mg/L, respectively — increases of 48%, 121%, 71%, and 12%. Application of 8 mg/L naproxen further enhanced catharanthine, vindoline, and vinblastine levels to 3.78, 0.67, and 2.14 mg/L, representing increases of 151%, 135%, and 30%, respectively. The Cu-CS complex at 10 mg/L elevated catharanthine, vindoline, ajmalicine, and vinblastine to 2.13, 0.49, 32.11, and 2.46 mg/L, with corresponding increases of 49%, 63%, 55%, and 36%. Notably, the combined treatment of all three agents synergistically boosted catharanthine, vindoline, and vinblastine production to 5.94, 1.52, and 3.65 mg/L — representing 310%, 390%, and 98% increases over control levels. Quantitative RT-PCR analysis revealed that Cu-CS treatment upregulated the transcription of key genes and transcription factors involved in terpenoid indole alkaloid (TIA) biosynthesis. Overall, this integrated strategy effectively redirects metabolic flux toward enhanced TIA production in C. roseus CMCs, providing a practical and efficient approach for improving the yield of pharmaceutically important alkaloids in plant cell culture systems.
研究领域:
植物生物技术
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次生代谢
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医药生物技术
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分子生物学
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代谢工程
✓ 已验证
产品关联
DOI
高影响因子
危险品化学品经营许可证（带存储）