International Journal of Biological Sciences
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2022
·
IF 10.75
Li Zhang,Linyu Zhu,Xiaohan Yao,Xiaohan Lou,Jiajia Wan,Xixi Duan,Longze Pan,Anqi Li,Zhuoyu Gu,Ming Wang,Fazhan Wang,Zhihai Qin
Chemotherapeutic drugs have been successfully used to treat several cancers, including melanoma. However, metastasis occasionally occurs after chemotherapy. Here, we reported that paclitaxel (PTX) treatment for B16F10 tumour in mice led to an enhanced lymphatic metastasis of the melanoma cells, although a significant inhibition of tumour growth at the injection site was observed. Further study demonstrated that PTX upregulated the expression of C-C chemokine receptor type 7 (CCR7) in B16F10 cells, enhancing their migration through the activation of JNK and p38 signalling pathways. Loss of CCR7 or blockade of C-C motif chemokine ligand 21 (CCL21)/CCR7 axis abolished the pro-migration effect of PTX on B16F10 melanoma cells. Importantly, combination of PTX and CCR7 mAb could simultaneously delay the tumour growth and reduce the lymphatic metastasis in B16F10 melanoma. The blockade of CCL21/CCR7 axis may collectively serve as a strategy for lymphatic metastasis in some melanoma after chemotherapy.
研究领域:
肿瘤学
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免疫学
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药理学
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PubMed
高影响因子
PROCESS BIOCHEMISTRY
·
2021
·
IF 3.757
Yonghua Hu,Yuan Zhou,Xiaohua Hu,Qiaoling Chen,Yan Shi,Jiangxing Zhuang,Qin Wang
Cefotaxime sodium (CTX) was found to inhibit the activity of mushroom tyrosinase. The present study was conducted to investigate its inhibition of melanogenesis in B16F10 cells. CTX was found to inhibit melanin synthesis in B16F10 cells at a concentrations less than 200 μmol/L with no cytotoxicity. CTX reduced tyrosinase activity in a dose-dependent manner. CTX inhibited melanin formation from the results of the Masson-Fontana melanin staining and transmission electron microscope CTX influenced melanin production by influencing the expression of the proteins MITF, TRP-1, TRP-2 and TYR. Furthermore, CTX could down-regulate the intracellular cAMP/PKA/CREB contents, affecting the expression of MITF, and further down-regulate the expression of TRP-1, TRP-2 and TYR to inhibit melanin. Furthermore, CTX has been shown to inhibit body pigmentation in zebrafish. These results may provide a theoretical foundation for the new application of CTX in the field of medicine.
研究领域:
药理学
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细胞生物学
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分子生物学
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DOI
高影响因子
Food & Function
·
2022
·Vol. 14
·期 2
·796-809
·
IF 6.317
Ni-Na Xie,Cheng-Ying Wu,Qiong Ge,Jing Zhou,Fang Long,Qian Mao,Song-Lin Li,Hong Shen
Ginseng polysaccharides (GPs) have shown gut microbiota-related antitumor effects. However, the relation between their structures and antitumor functions remains unknown. Here, crude polysaccharide (GP-c) and its fractions neutral polysaccharide (GP-n) and pectin (GP-a) were prepared for structure characterization and anti-B16F10 melanoma effect evaluation, and their influence on gut microbiota diversities and short-chain fatty acids (SCFAs) were also analyzed. Spearman correlations among the altered gut microbiota, SCFAs, and antitumor effects were conducted to elucidate the structure–function relationships. It was shown that the structures of GP-c, GP-n, and GP-a varied in monosaccharide composition and molecular weight distribution. GP-n and GP-c showed anti-melanoma effects, whereas GP-a promoted its growth slightly. GP-n and GP-c restored SCFAs levels such as acetic acid and butyric acid; moreover, it improved the gut microbiota ecosystem by upregulating the abundance of Allobaculum and Bifidobacterium. However, the restoration effect of GP-a was weak, or even worse. In addition, these two bacteria were negatively correlated with the tumor weight and related with the altered SCFAs. In conclusion, GP-n is essential for the anti-melanoma effects of GP, and the potential mechanisms might be related with its specific regulation of Allobaculum and Bifidobacterium abundance, and tumor-associated SCFAs levels. The outcomes highlighted here enable a deeper insight into the structure–function relationship of GP and propose new opinions on its antitumor effect.
研究领域:
药理学
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肿瘤学
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微生物学
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分子生物学
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DOI
PubMed
高影响因子
PROTEIN JOURNAL
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2021
·Vol. 40
·期 5
·709-720
·
IF 2.371
Jiang Xuan,Zhang Xin,Fu Chao,Zhao Ruili,Jin Tianming,Liu Mengyue,Pan Chenhao,Li Liu An,Ma Jifei,Yu Enyuan,YU Xiaoxue,Hu Ye
Malignant melanoma, an increasingly common form of skin cancer, poses a significant threat to public health, especially when the disease progresses past skin lesions to the stage of advanced metastasis. In this work, a new anti-tumor peptide, temporin La (T-La), was selected from a cDNA library generated from bullfrog skin. Two new derivative antitumor peptides, T-La (S) and T-La (FS), were designed by bioinformatics analysis and coupled with the RGD small molecule peptide to create chimeric RGD peptides, (RGD-T-La [S] and RGD-T-La [FS]). Preliminary experiments showed that the new antitumor peptides had significant antitumor effects. After coupling to the chimeric RGD peptide, the targeted treatment of mouse melanoma was significantly improved. Our data demonstrate that the 4 peptides tested herein significantly inhibited the proliferation, migration, and invasion of B16F10 cells; with an increase in polypeptide concentration, the proportion of melanoma cells in the G0/G1 phase decreased or increased significantly, respectively, the reactive oxygen species (ROS) content increased significantly, the mitochondrial membrane potential decreased significantly, and the expression of pro-apoptotic Bax, Caspase-3, and Caspase-9 increased, and anti-apoptotic Bcl-2 decreased significantly. Tyr and MITF genes were significantly downregulated. In conclusion, the use of these new anti-tumor peptides, when combined with a chimeric RGD peptide, may increase ROS levels and decrease mitochondrial membrane potential by inhibiting the activity of mitochondria, thus releasing apoptosis-promoting factors in B16F10 cells. The present study describes a new potential strategy for the application of promising peptides in the treatment of various cancers.
研究领域:
肿瘤学
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药理学
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分子生物学
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细胞生物学
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF DRUG DELIVERY SCIENCE AND TECHNOLOGY
·
2026
·
IF 5.2
Xia Cao,Zhangxintian Ding,Yize Lv,Xuedi Weng,Hongran Huang,Jinghan Li,Ximing Xu,Qilong Wang
The clinical treatment of melanoma is severely limited by the rapid development of intrinsic and acquired resistance to conventional chemotherapeutic drugs, such as doxorubicin (DOX), as well as their severe, dose-limiting systemic toxicities. To address this issue, we developed a novel nanoplatform for near-infrared (NIR)- activatable nanoplatform leveraging microfluidics as a precision fabrication tool to overcome the limitations of conventional nanocarrier synthesis, including poor batch-to-batch reproducibility, heterogeneous size distribution, and suboptimal drug co-loading. A photocrosslinkable copolymer, Pluronic F127 diacrylate (F127DA), was synthesized and processed using a custom-designed dual-zone microfluidic chip that integrates sequential flow-focusing and turbulent mixing. This approach enabled the one-step, highly controlled co-encapsulation of DOX and indocyanine green (ICG) into monodisperse F127DA nanoparticles (43.9 ± 0.6 nm, polydispersity index: 0.18) with superior encapsulation efficiency (DOX: 60.4%) and drug loading (12.8%). Upon NIR irradiation, the resulting DOX/ICG@F127DA nanoparticles mediated synergistic chemo-photothermal-photodynamic therapy, as evidenced by potent cytotoxicity (melanoma cell viability reduced to 35%), a significant 3.1-fold increase in reactive oxygen species (ROS) generation, and effective inhibition of cell migration (wound closure rate of 17.2% compared to 21.7% with free DOX). Mechanistically, the NIR-triggered ROS burst induced mitochondrial-mediated apoptosis by dysregulating the Bax/Bcl-2 ratio (increased by 2.7-fold), culminating in an apoptosis rate of up to 68.3%. Collectively, this work establishes microfluidics as a robust and scalable platform for engineering complex nanomedicines and delineates the “NIR light–ROS–Bax/Bcl-2” axis as a critical molecular pathway for overcoming chemoresistance in melanoma. Download: Download high-res image (231KB) Download: Download full-size image
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高影响因子
Food & Function
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2018
·Vol. 9
·期 9
·5007-5015
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IF 3.289
Zheng-Nan Cai,Wan Li,Shomaila Mehmood,Wen-Juan Pan,Qing-Xi Wu,Yan Chen,Yong-Ming Lu
Polysaccharides from Morchella esculenta are known to exhibit diverse bioactivities, while an anti-melanogenesis effect has been barely addressed. Herein, the anti-melanogenesis activity of a heteropolysaccharide from M. esculenta (FMP-1) was investigated in vitro and in vivo. FMP-1 had no significant cytotoxic effect on B16F10 melanoma cells as well as zebrafish larvae, but did reduce melanin contents and tyrosinase activities in both of them. Treatment with FMP-1 also effectively suppressed the expression of melanogenesis-related proteins, including MC1R, MITF, TRP-1 and TRP-2, through decreasing the phosphorylation of cyclic adenosine monophosphate response element-binding protein (CREB). Moreover, the mitogen-activated protein kinase (MAPK) pathway was observed mediating FMP-1's inhibitory effect against melanin production. Specifically, FMP-1 treatment markedly inhibited the activation of phosphorylation of p38 mitogen-activated protein kinase. These results suggested that FMP-1's inhibitory effect against melanogenesis is mediated by the inhibition of CREB and p38 signaling pathways, thereby resulting in the downstream repression of melanogenesis-related proteins and the subsequent melanin production. These data provide insight into FMP-1's potential anti-melanogenesis effect in food and cosmetic industries.
研究领域:
药理学
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细胞生物学
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化妆品科学
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DOI
PubMed
高影响因子
BRAZILIAN JOURNAL OF MEDICAL AND BIOLOGICAL RESEARCH
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2018
·
IF 1.492
Liu Zi-Jun,Wang Ya-Lan,Li Qi-Ling,Yang Liu
Cuscuta chinensis polysaccharide (CPS) was extracted using hot water and enzymatically hydrolyzed C. chinensis polysaccharide (ECPS) was produced by the mannase enzymatic hydrolysis process. The purpose of this research was to investigate the antimelanogenic activity of ECPS and CPS in B16F10 melanoma cells. The in vitro antioxidant activity was assessed by their ferric iron reducing power and DPPH free radical scavenging activities. The molecular mass distribution of polysaccharides was determined using SEC-MALLS-RI. CPS was successfully enzymatically degraded using mannase and the weighted average molecular weights of CPS and ECPS were 434.6 kDa and 211.7 kDa. The results of biological activity assays suggested that the enzymatically hydrolyzed polysaccharide had superior antimelanogenic activity and antioxidant effect than the original polysaccharide. ECPS exhibited antimelanogenic activity by down-regulating the expression of tyrosinase, MITF, and TRP-1 without cytotoxic effects in B16F10 melanoma cells. In conclusion, ECPS have the potential to become a skin whitening product.
研究领域:
生物化学
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药理学
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化妆品科学
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DOI
PubMed
高影响因子
Chemistry-An Asian Journal
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2021
·Vol. 16
·期 19
·2993-3000
·
IF 4.568
Pan Wang,Jian-Wei Wang,Wen-Hua Zhang,Hongzhen Bai,Guping Tang,David J. Young
Graphical Nanoformulations of a class of mononuclear and dinuclear Pt-based complexes bearing Pt−P bonds have been developed as efficient chemotherapeutic reagents against murine melanoma cell line B16F10. Nanoformulations of mononuclear Pt complexes cis -PtCl 2 (PPh 3 ) 2 ( 1 ), [Pt(PPh 3 ) 2 (L−Cys)] ⋅ H 2 O ( 3 , L−Cys=L-cysteinate), trans -PtCl 2 (PPh 2 PhNMe 2 ) 2 ( 4 ; PPh 2 PhNMe 2 =4-(dimethylamine)triphenylphosphine), trans -PtI 2 (PPh 2 PhNMe 2 ) 2 ( 5 ) and dinuclear Pt cluster Pt 2 ( μ -S) 2 (PPh 3 ) 4 ( 2 ) have comparable cytotoxicity to cisplatin against murine melanoma cell line B16F10. Masking of these discrete molecular entities within the hydrophobic core of Pluronic® F-127 significantly boosted their solubility and stability, ensuring efficient cellular uptake, giving in vitro IC 50 values in the range of 0.87–11.23 μM. These results highlight the potential therapeutic value of Pt complexes featuring stable Pt−P bonds in nanocomposite formulations with biocompatible amphiphilic polymers.
研究领域:
药理学
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肿瘤学
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纳米医学
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DOI
高影响因子
Chinese Journal of Natural Medicines
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2018
·
IF 1.991
Rakotomalala Manda Heriniaina,Jing DONG,Praveen Kumar Kalavagunta,Hua-Li WU,Dong-Sheng YAN,Jing SHANG
Several chemical compounds can restore pigmentation in vitiligo through mechanisms that vary according to disease etiology. In the present study, we investigated the melanogenic activity of six structurally distinct compounds, namely, scopoletin, kaempferol, chrysin, vitamin D 3 , piperine, and 6-benzylaminopurine. We determined their effectiveness, toxicity, and mechanism of action for stimulating pigmentation in B16F10 melanoma cells and in a zebrafish model. The melanogenic activity of 6-benzylaminopurine, the compound identified as the most potent, was further verified by measuring green fluorescent protein concentration in tyrp1 a: eGFP (tyrosinase-related protein 1) zebrafish and mitfa: eGFP (microphthalmia associated transcription factor) zebrafish and antioxidative activity. All the tested compounds were found to enhance melanogenesis responses both in vivo and in vitro at their respective optimal concentration by increasing melanin content and expression of TYR and MITF. 6-Benzyamino-purine showed the strongest re-pigmentation action at a concentration of 20 μmol·L −1 in vivo and 100 μmol·L −1 in vitro , and up-regulated the strong fluorescence expression of green fluorescent protein in tyrp1a: eGFP and mitfa: eGFP zebrafish in vitro . However, its relative anti-oxidative activity was found to be very low. Overall, our results indicated that 6-benzylaminopurine stimulated pigmentation through a direct mechanism, by increasing melanin content via positive regulation of tyrosinase activity in vitro , as well as up-regulating the expression of the green fluorescent protein in transgenic zebrafish in vivo .
研究领域:
药理学
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皮肤病学
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分子生物学
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产品关联
DOI
PubMed
高影响因子
International Journal of Nanomedicine
·
2026
·
IF 8.7
Hao Ding,Dan li Li,Zi yi Zhou,Xiang Dong Lai,Nan Yang,Liu chang Tan,Yuan gang Lu
Background Malignant melanoma is a highly aggressive skin cancer. Dacarbazine (DTIC) chemotherapy, while historically used, is limited by poor solubility, short half-life, and systemic toxicity. Fe3O4 nanoparticles have been explored as drug delivery vectors with potential for photothermal conversion and Fenton-like catalytic activity. Cell membrane-camouflaged platforms may offer improved tumor targeting.Methods A biomimetic nanoplatform (Fe3O4PD@CCM) was engineered by encapsulating an Fe3O4 core within a DTIC-loaded PLGA-PEG2000 matrix, followed by functionalization with B16F10 cancer cell membranes. Physicochemical properties were characterized by dynamic light scattering (DLS), scanning electron microscopy (SEM), and liquid chromatography–mass spectrometry (LC-MS). Antitumor effects were assessed in B16F10 melanoma cells and in a subcutaneous syngeneic mouse model (n=4 per group).Results Fe3O4PD@CCM Nanoparticles (NPs) exhibited a hydrodynamic diameter of ~25–30 nm, sustained DTIC release, and retention of membrane proteins. In vitro, the Fe3O4PD@CCM + NIR (Near-infrared irradiation) group showed reduced cell viability, increased apoptosis, G2/M phase arrest, and elevated intracellular reactive oxygen species (ROS) levels compared to controls. In vivo, Cy5-labeled Fe3O4PD@CCM NPs showed preferential fluorescence accumulation in tumors relative to non-coated NPs, with whole-body fluorescence diminishing within 24 h. In a 12-day efficacy study, Fe3O4PD@CCM + NIR treatment was associated with reduced tumor growth compared to control groups. Acute biosafety assessment at 24 h post-injection of a single high dose (200 mg/kg) revealed no overt abnormalities in the evaluated hematological, biochemical, or histopathological parameters.Conclusion Fe3O4PD@CCM NPs combined with NIR suppressed B16F10 cell activity in vitro and subcutaneous tumor growth in a preliminary mouse model. These findings represent a proof-of-concept demonstration. Further studies—including detailed mechanistic validation, long-term toxicity assessment, and evaluation in more clinically relevant models—are required to assess the translational potential of this platform.
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DOI
高影响因子
Medicinal Chemistry
·
2017
·Vol. 13
·期 8
·753-760
·
IF 2.331
Guo Ping,Xie Zixin,Zhang Huan,Zhang Zaikui,Han Chao,Cheng Donghua,Lin Dan,Zhang Yuan,Wang Xuebao,Guo Xin,Ye Faqing
Background: Thienopyrimidinone is a newly designed, selective fibroblast growth factor receptor 1 (FGFR1) inhibitor with an excellent anticancer effect. Objective: The goal of the present study was to design and synthesize better FGFR1 inhibitors through modifications of the lead
compound thienopyrimidinone. Methods: In the present study, a series of C-2 substituted derivatives of thienopyrimidinone, namely L1-L16, were synthesized, and their inhibitory effects on FGFR1 were evaluated. The anti-proliferative activities of these compounds were assessed by MTT assay.
Results: Among the novel derivatives, L11 was found to exert remarkable FGFR1 inhibitory activity (79.93% at 10 μM) and anti-proliferative activity, with IC50 values of 2.1, 2.5, and 3.5 µM in the FGFR1-overexpressing cell lines, H460, HT-1197, and B16F10, respectively.
Conclusion: Our newly synthesized thienopyrimidinone derivatives may be candidate FGFR1 inhibitors for future development as novel anticancer agents.
研究领域:
药理学
·
肿瘤学
·
药物化学
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DOI
PubMed
高影响因子
BIOORGANIC CHEMISTRY
·
2024
·
IF 4.5
Shulei Qi,Lina Guo,Jinxin Liang,Kaixuan Wang,Qinghong Liao,Siyu He,Weiping Lyu,Zimeng Cheng,Jiayi Wang,Xiaojia Luo,Xiaomei Yan,Ziyao Lu,Xiaohan Wang,Ziming Wang,Xuehong Chen,Qi Li
The high level of tyrosinase leads to the generation of neuromelanin, further causing the abnormality of redox-related protein level and mediating the occurrence and development of Parkinson’s disease (PD). However, the existing tyrosinase inhibitors are mostly natural product extracts or polyphenolic derivatives, which hindered them from penetrating the blood–brain barrier (BBB). Herein, we obtained a novel tyrosinase inhibitor, 2-06 (tyrosinase: monophenolase IC 50 = 70.44 ± 22.69 μM, diphenolase IC 50 = 1.89 ± 0.64 μM), through the structure-based screening method. The compound 2-06 presented good in vitro and in vivo safety, and can inhibit the tyrosinase and melanogenesis in B16F10. Moreover, this compound showed neuroprotective effects and Parkinsonism behavior improving function. 2-06 was proved to penetrate the BBB and enter the central nervous system (CNS). The exploration of the binding mode between 2-06 and tyrosinase provided the foundation for the subsequent structural optimization. This is the first research to develop a central-targeting tyrosinase inhibitor, which is crucial for in-depth study on the new strategy for utilizing tyrosinase inhibitors to treat PD.
研究领域:
神经学
·
药理学
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药物开发
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DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）