TREE PHYSIOLOGY
·
2017
·Vol. 37
·期 12
·1659-1671
·
IF 3.653
Yu Chunna,Guo Hong,Zhang Yangyang,Song Yaobin,Pi Erxu,Yu Chenliang,Zhang Lei,Dong Ming,Zheng Bingsong,Wang Huizhong,Shen Chenjia
Taxol is currently a valuable anticancer drug; however, the accumulated mixture of taxoids can vary greatly among Taxus species. So far, there is very little genomic information for the genus Taxus, except for Taxus baccata. Transcriptome analysis is a powerful approach to explore the different regulatory mechanisms underlying the taxoid biosynthesis pathway in Taxus species. First, we quantified the variation in the taxoid contents between Taxus media and Taxus mairei. The contents of paclitaxel and 10-deacetylpaclitaxel in T. media are higher than that in T. mairei. Then, the transcriptome profiles of T. media and T. mairei were analyzed to investigate the altered expressions. A total of 20,704 significantly differentially expressed genes (DEGs), including 9865 unigenes predominantly expressed in T. media and 10,839 unigenes predominantly expressed in T. mairei, were identified. In total, 120 jasmonic acid-related DEGs were analyzed, suggesting variations in ‘response to JA stimulus’ and ‘JA biosynthetic process’ pathways between T. media and T. mairei. Furthermore, a number of genes related to the precursor supply, taxane skeleton formation and hydroxylation, and C13-side chain assembly were also identified. The differential expression of the candidate genes involved in taxoid biosynthetic pathways may explain the variation in the taxoid contents between T. media and T. mairei.
研究领域:
植物科学
·
药理学
·
分子生物学
·
基因组学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Polymers
·
2019
·Vol. 11
·期 3
·511
·
IF 3.164
Jingjie Feng,Weiqiu Wen,Yong-Guang Jia,Sa Liu,Jianwei Guo
One of the most famous anticancer drugs, paclitaxel (PTX), has often been used in drug controlled-release studies. The polymers derived from bio-compound bile acids and degradable poly(ε-caprolactone) (PCL) form a reservoir and have been used as a drug delivery system with great advantages. Herein, we grafted poly(N,N-diethylaminoethyl methacrylate) and poly(poly(ethylene glycol) methyl ether methacrylate) into the bile acid-derived three-armed macroinitiator CA-(PCL)3, resulting in the amphiphilic block copolymers CA-(PCL-b-PDEAEMA-b-PPEGMA)3. These pH-responsive three-armed block copolymers self-assembled into micelles in aqueous solution and PTX was encapsulated into the micellar core to form PTX-loaded micelles with a drug loading of 29.92 wt %. The micelles were stable in PBS at pH 7.4 and showed a pH-triggered release behavior of PTX under acidic environments, in which 55% of PTX was released at pH 5.0 in 80 h. These cholic acid-based functionalized three-armed block polymers present good biocompatibility, showing great potential for drug controlled-release.Keywords:cholic acid;pH-sensitive;PTX;drug delivery
研究领域:
生物材料学
·
药剂学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
·
2023
·
IF 8.2
Chen Ying,Zhang Meng,Zhang Wenli,Wang Yamin,Zhang Hua,Yang Liu,Yu Longjiang,Fu Chunhua
Taxol, a valuable but rare secondary metabolite of the genus Taxus , is an effective anticancer drug. Understanding the regulation of taxol biosynthesis may provide a means to increase taxol content. The microRNA miR5298b was found to promote the accumulation of taxol and upregulate several taxol biosynthesis genes, including DBAT , TASY , and T5H , as demonstrated by experiments using the overexpression and mimicry of transient leaves. Moreover, miR5298b cleaves the mRNA sequence of TcNPR3 , a homolog of the salicylic acid receptor AtNPR3/4. Overexpression and knockdown by RNA interference of TcNPR3 confirmed that it repressed taxol biosynthesis. These results indicate that miR5298b enhances taxol biosynthesis via the cleavage of TcNPR3 . Yeast two-hybrid bimolecular fluorescence complementation and pull-down assays revealed that TcTGA6, a TGA transcription factor, physically interacted with TcNPR3. Functional experiments showed that TcTGA6 negatively regulates taxol biosynthesis by directly combining with the TGACG motif in the promoters of TASY , T5H , and T10H . TcNPR3 enhances TcTGA6 inhibition Luciferase assays showed that miR5298b alleviated the repression of the TcNPR3–TcTGA6 complex. In summary, miR5298b can cleave TcNPR3 , thereby alleviating the inhibition of the TcNPR3–TcTGA6 complex to upregulate taxol biosynthesis genes.
研究领域:
植物学
·
分子生物学
·
药理学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Regenerative Biomaterials
·
2021
·Vol. 8
·期 3
·
IF 6.353
Wang Qiaoying,Wu Changqiang,Li Xiaoting,Yang Dixiao,Shi Liangjun
We have designed and developed an effective drug delivery system using biocompatible polymer of poly (ethylene glycol)-polyaspartic acid (mPEG-PAsp) for co-loading the chemotherapy drugs paclitaxel (PTX) and cisplatin (CP) in one nano-vehicle. This study aimed to improve the anti-cancer efficacy of combinations of chemotherapy drugs and reduce their side effects. mPEG-PAsp-(PTX/Pt) nano-micelles disperse well in aqueous solution and have a narrow size distribution (37.8 ± 3.2 nm) in dynamic light scattering (DLS). Drug release profiles found that CP released at pH 5.5 was significantly faster than that at pH 7.4. MPEG-PAsp-(PTX/Pt) nano-micelles displayed a significantly higher tumor inhibitory effect than mPEG-PAsp-PTX nano-micelles when the polymer concentrations reached 50 μg/mL. Our data indicated that polymer micelles of mPEG-PAsp loaded with the combined drug exert synergistic anti-tumor efficacy on SKOV3 ovarian cells via different action mechanisms. Results from our studies suggested that mPEG-PAsp-(PTX/Pt) nano-micelles are promising alternatives for carrying and improving the delivery of therapeutic drugs with different water solubilities.
研究领域:
药学
·
肿瘤学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
INDUSTRIAL CROPS AND PRODUCTS
·
2020
·
IF 4.244
Min Shi,Yao Wang,Xiaorong Wang,Changping Deng,Wenzhi Cao,Qiang Hua,Guoyin Kai
Tanshinones and phenolic acids are two major groups of natural bioactive compounds in Salvia miltiorrhiza which exert excellent pharmacological activities. Due to low content in S.miltiorrhiza , it is urgent to enhance the production of the two compounds to meet the increasing need. The Arabidopsis basic helix-loop-helix (bHLH) transcription factor MYC2 was introduced into S. miltiorrhiza hairy roots. In the best transgenic line AtMYC2-3 , tanshinone yield was 14.06 mg/g dw which was increased by 5.45-fold more than that in the control line, while phenolic acid production was enhanced to 95.9 mg/g dw, a 3.3-fold increase compared with the control. Transcript levels of some genes involved in biosynthesis of tanshinones and phenolic acids were noticeably upregulated. Dual-luciferase assay revealed that AtMYC2 activated the expression of biosynthetic genes including SmDXS2 and SmTAT . These results revealed that AtMYC2 plays a positive role in accumulation of both tanshinones and phenolic acids which provides a promising strategy for engineering tanshinone and phenolic acid production in S. miltiorrhiza .
研究领域:
植物学
·
分子生物学
·
药用植物学
✓ 已验证
产品关联
DOI
高影响因子
DRUG DEVELOPMENT RESEARCH
·
2025
·Vol. 86
·期 2
·e70047
·
IF 4.2
Kangmin Chen,Yanni Zhao,Tianyang Jin,Tingxin Xu,Conglun Zhu,Hui Shen,Xiaohong Xu,Yongsheng Jiang,Yi Wang,Shihang Xue
Triple-negative breast cancer (TNBC) is difficult to treat due to the lack of clear therapeutic targets. Paclitaxel (PTX) is commonly used to treat TNBC, but drug resistance limits its effectiveness. Myeloid differentiation protein 2 (MD2) and serum amyloid A1 (SAA1) are involved in various diseases, including infections, inflammatory diseases, and cancer. We investigated their role in PTX resistance to identify potential anti-TNBC drugs. In this study, we investigated the changes of SAA1 in TNBC tissues and its role in PTX-induced TNBC cells. Our study revealed SAA1 expressed in the human TNBC subtype and TNBC cells. PTX and CIS induce SAA1 in TNBC cells, and PTX induces inflammatory response via SAA1 in TNBC cells. MD2 blockade increased the sensitivity of TNBC cells to PTX, which was related to the expression of SAA1 during PTX-caused damage of TNBC cells. In further research, SAA1 binds to MD2, promotes the combination of TLR4/MD2 and TLR4/MyD88, activates the NF-κB signaling pathway, and creates the inflammatory microenvironment for cancer cells. Our study reports for the first time that the PTX/SAA1/MD2 axis exists in the PTX-resistance process, which could be a potential treatment target of PTX-resistance.
研究领域:
肿瘤学
·
免疫学
·
药理学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
BIOORGANIC & MEDICINAL CHEMISTRY
·
2022
·
IF 3.461
Chunyan Yang,Zhongzhen Yang,Siqi Wang,Jinxia Chen,Qijun Liu,Tianle Huang,Li Hai,Runxin Lu,Yong Wu
Chemotherapy is a conventional treatment for glioma, but its efficacy is greatly limited due to low blood–brain barrier (BBB) permeability and lack of specificity. Herein, intelligent and tumor microenvironment (TME)-responsive folic acid (FA) derivatives and mitochondria-targeting berberine (BBR) derivatives co-modified liposome coated with Tween 80 loading paclitaxel (PTX-Tween 80-BBR + FA-Lip) was constructed. Specifically speaking, liposomes modified by FA can be effectively target ed to glioma cells. BBR, due to its delocalized positive electricity and lipophilicity, can be attracted by mitochondrial membrane potential and concentrate on mitochondria to achieve mitochondrial targeting and induce cell apoptosis. By simultaneously modifying the liposome with FA and BBR to deliver drugs, leads to a good therapeutic effect of glioma through FA-based glioma targeting and BBR-based mitochondrial targeting. In addition, the surface of the liposome was coated with Tween 80 to further improve BBB penetration. All results exhibited that PTX-Tween 80-BBR + FA-Lip can observably improve the chemotherapy therapeutic efficacy through the highly specific tumor targeting and mitochondrial targeting, which can provide new ideas and methods for the targeted therapy of glioma.
研究领域:
药学
·
神经肿瘤学
·
药物递送系统
·
纳米技术
·
癌症治疗
✓ 已验证
产品关联
DOI
PubMed
高影响因子
COLLOIDS AND SURFACES B-BIOINTERFACES
·
2025
·
IF 5.6
Qianqian Zhao,Ting Wu,Chunming Tang,Jie Li,Min Wu,Jie Wu,Zhiji Wang,Yinxin Zhu,Huae Xu,Xiaolin Li
Combination chemotherapy is considered more effective than monotherapy in enhancing clinical outcomes. Ferroptosis, a unique form of regulated cell death, has been demonstrated to inhibit tumor growth and progression. Consequently, combining ferroptosis with chemotherapy represents a promising and innovative approach to antitumor therapy. In this study, we developed a novel TMTP1-modified biomimetic nanocrystal (TRNC@P + L) for the co-delivery of PTX and LF3, aiming to achieve ferroptosis-combined chemotherapy in gastric cancer. TRNC@P + L, which incorporates a tumor-homing peptide-modified red blood cell membrane, demonstrated efficient tumor targeting, prolonged circulation, enhanced drug bioavailability, and reduced non-specific toxicities of free PTX and LF3. By utilizing the synergistic effects of PTX and LF3, TRNC@P + L combination therapy significantly inhibited tumor growth, as demonstrated by both in vitro and in vivo studies. Mechanistically, TRNC@P + L triggers ferroptosis in tumor cells by downregulating GPX4 expression, the promotion of ROS accumulation, and the enhancement of lipid peroxidation. These processes synergistically enhance the anticancer efficacy of PTX.
研究领域:
肿瘤学
·
药理学
·
纳米医学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
·
2018
·
IF 2.559
Jianhao Xu,Cunjin Su,Fenglun Zhao,Jialong Tao,Duanmin Hu,Aiming Shi,Jie Pan,Yusong Zhang
Paclitaxel (PTX) is a first-line chemotherapy drug for advanced non-small cell lung cancer (NSCLC). The long-chain non-coding RNA maternally expressed gene 3 (MEG3) is a recognized tumor suppressor . This study aimed to explore the effects of PTX on the expression of MEG3 and its anti-tumor mechanism in lung cancer cells. 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assays were performed to determine cell proliferation . Quantitative polymerase chain reaction was used to determine the levels of MEG3 expressions. Western blot and immunofluorescence were used to detect protein levels. Small interfering RNA or pCDNA-MEG3 transfection was used to downregulate or upregulate MEG3 expression. Dichlorof luorescein diacetate was used to detect intracellular reactive oxygen species. Flow cytometry was used to analyze apoptosis. PTX significantly inhibited the proliferation of NSCLC cells and increased the expressions of MEG3 and P53. The downregulation of MEG3 attenuated PTX-induced cytotoxicity, whereas upregulation of MEG3 induced cell death and increased P53 expression. The inhibition of P53 caused no effect on the upstream MEG3 expression. Our results suggest that the MEG3-P53 pathway is involved in the apoptosis of A549 cells induced by PTX.
研究领域:
肿瘤学
·
分子生物学
·
药理学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
MACROMOLECULAR BIOSCIENCE
·
2016
·Vol. 16
·期 5
·774-783
·
IF 3.68
Tieshi Wang,Xinde Tang,Jingtian Han,Yuanyuan Ding,Wenjuan Guo,Meishan Pei
Biodegradable self-assembled polymeric nanoparticles (NPs) composed of poly(6- O -methacryloyl-D-galactopyranose)- b -poly(L-lactide)- b -poly(6- O -methacryloyl-D-galactopyranose) (PMAGP- b -PLA- b -PMAGP) are prepared as carriers for the hydrophobic anticancer drug paclitaxel (PTX), to achieve target delivery to hepatoma cells. PTX can be encapsulated by the NPs with various molar ratios of L-lactide (LA) and 6- O -methacryloyl-D-galactopyranose (MAGP) during the process of self-assembly, and the resulting NPs exhibit high drug loading efficacy and substantial stability in aqueous solution. The size, size distribution, and morphology of the NPs are characterized using a Zetasizer Nano ZS and transmission electron microscopy. The hemolysis assay and cell cytotoxicity assay indicate that the polymeric NPs are biocompatible and non-toxic. The cellular uptake assay demonstrates that the galactose-containing NPs can be selectively recognized and subsequently accumulate in HepG2 cells. All of these results demonstrate that galactose-containing polymeric NPs are potential carriers for hepatoma-targeted drug delivery and liver cancer therapy in clinical medicine.
研究领域:
药剂学
·
肿瘤学
·
生物材料学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Pharmaceutics
·
2023
·Vol. 15
·期 7
·1874
·
IF 5.4
Heming Zhao,Liming Gong,Hao Wu,Chao Liu,Yanhong Liu,Congcong Xiao,Chenfei Liu,Liqing Chen,Mingji Jin,Zhonggao Gao,Youyan Guan,Wei Huang
Prostate cancer (PC) is one of the common malignant tumors of the male genitourinary system. Here, we constructed PTX@ZIF-8, which is a metal-organic-framework-encapsulated drug delivery nanoparticle with paclitaxel (PTX) as a model drug, and further modified the synthesized peptide dimer (Di-PEG2000-COOH) onto the surface of PTX@ZIF-8 to prepare a nanotargeted drug delivery system (Di-PEG@PTX@ZIF-8) for the treatment of prostate cancer. This study investigated the morphology, particle size distribution, zeta potential, drug loading, encapsulation rate, stability, in vitro release behavior, and cytotoxicity of this targeted drug delivery system, and explored the uptake of Di-PEG@PTX@ZIF-8 by human prostate cancer Lncap cells at the in vitro cellular level, as well as the proliferation inhibition and promotion of apoptosis of Lncap cells by the composite nanoparticles. The results suggest that Di-PEG@PTX@ZIF-8, as a zeolitic imidazolate frameworks-8-loaded paclitaxel nanoparticle, has promising potential for the treatment of prostate cancer, which may provide a novel strategy for the delivery system targeting prostate cancer.Keywords:metal-organic framework;paclitaxel;peptide dimer;prostate cancer
研究领域:
药学
·
肿瘤学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF COLLOID AND INTERFACE SCIENCE
·
2017
·
IF 4.233
Tao Zhang,Wei Zhang,Min Zheng,Zhigang Xie
Self-assembly of organic molecules has attracted more and more attention because of precise molecular structure and multifarious synthesis chemistry . Herein, near-infrared brominated boron-dipyrromethenes (BODIPY) paclitaxel conjugate (BrBDP-2PTX) was synthesized. BrBDP-2PTX could self-assemble into uniform spherical nanoparticles (BrBDP-2PTX NPs) via nanoprecipition method. The obtained nanoparticles showed satisfying stability in aqueous solution and 10% fetal bovine serum (FBS) containing phosphoric acid buffer solution (PBS). Moreover, BrBDP-2PTX NPs could make rapid enzyme response to Proteinase K as evidenced by the obvious changes in size and size distribution. BrBDP-2PTX NPs could be internalized by the HeLa cells and exhibited potent cytotoxicity toward tumor cells (human cervical carcinoma cells and liver hepatocellular carcinoma cells) as revealed by 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide (MTT) assays and live/dead staining. Furthermore, in vivo experiments indicated BrBDP-2PTX NPs could be used as efficient bioimaging agents without causing any systemic toxicity. This work highlights the potential of using self-assembly of small organic molecules to develop functional nanomaterials .
研究领域:
药剂学
·
肿瘤学
·
生物医学工程
✓ 已验证
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）