JOURNAL OF ELECTROANALYTICAL CHEMISTRY
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2020
·
IF 3.807
Anzi Yang,Xiaoxia Huangfu,Lixiao Liu,Wen Luo,Wenbo Zhao,Jun Yin
Biomedical detection needs to develop more detection methods and reagents. CuFeS 2 , an I-III-IV ternary semiconductor material, has attracted great interest of researchers because of its optical, electrical, low toxicity and controllable chemical synthesis. Here, we synthesized CuFeS 2 quantum dots (QDs) with hot-injection method and their ECL behaviors were investigated for the first time, involving the co-reactant anode/cathode ECL emission and the related ECL mechanism. Moreover, a novel ECL immunosensor based on CuFeS 2 QDs for the ultrasensitive detection of Cyclin D1 (CCND1) was designed and prepared. CuFeS 2 QDs with uniform size and excellent optical properties were used as ECL emitters and Carboxyl Fe 3 O 4 magnetic beads (MB) were utilized for magnetic separation of CCND1 from MCF-7 cells treated by sophora frevescens. In addition, reduced graphene oxide (rGO) and Au NPs by electrodeposition not only provided plentiful active sites for the immobilization of anti-CCND1 (primary antibody, Ab 1 ), but also enhanced the conductivity of the electrode. Results indicated that under the optimal condition, the ECL signal was proportional to the logarithmic of CCND1 concentration in the linear range from 40 fg/mL to 0.8 μg/mL with a detection limit of 15.8 fg/mL. Further, the good reproducibility, stability and selectivity of the as-prepared ECL immunosensor were also proved. Significantly, the anticancer effect of sophora frevescens on MCF-7 cells was investigated through quantitative analysis of overexpression of CCND1, which was related to proliferation of cancer cells. This research indicated the ECL immunosensor we suggested could offer great potential for the follow-up research in clinical diagnosis and anticancer drug screening.
研究领域:
生物医学工程
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分析化学
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材料科学
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肿瘤学
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DOI
高影响因子
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
·
2026
·Vol. 27
·期 3
·1228
·
IF 4.9
Ruifang Guo,Yihang Wang,Aiwen Zhang,Siwanon Jirawatnotai,Chen Chu,Lijun Liu
Beyond their canonical role in promoting G1/S progression, the complexes formed by cyclin D and cyclin-dependent kinase (CDK) 4/6 have emerged as contributors to enhanced cell migration. However, a direct link between this complex and cytoskeletal remodeling during cell motility has remained poorly understood. Here, we show that CDK4/6 inhibition in HeLa cells disrupts lamellipodia formation and subsequent focal adhesion assembly, leading to a reduction in cell migration and invasion. Notably, CDK4, but not CDK6, in complex with cyclin D1/D2, localizes to membrane ruffles to facilitate cytoskeletal reorganization. Mechanistically, proteomic and phosphoproteomic analyses revealed that CDK4 inhibition attenuates the transforming growth factor β (TGFβ) pathway via reduced Smad3 phosphorylation at Thr8, downregulating integrin subunits (α5, α6, and β1). Furthermore, CDK4 inhibition significantly decreased focal adhesion kinase (FAK) phosphorylation at Tyr397 and Rac1-GTP levels. Importantly, the resulting migration defect was largely restored by activation of either Rac1 or FAK. Thus, our data support a model in which cyclin D1/D2–CDK4 promotes phosphorylation of Smad3, leading to upregulation of integrin subunits, activation of FAK and Rac1, and consequent lamellipodia formation and cell migration. These findings provide direct evidence that CDK4 regulates actin cytoskeletal reorganization during cell migration and suggest that CDK4/6 inhibitors may dampen cytoskeleton-dependent tumor invasion, in addition to their antiproliferative effects.
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PubMed
高影响因子
MOLECULES
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2018
·Vol. 23
·期 7
·1578
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IF 3.098
Wenrui Wang,Tiantian Chen,Henan Xu,Baihui Ren,Xiaodan Cheng,Rongrong Qi,Haibo Liu,Yueyue Wang,Lei Yan,Sulian Chen,Qingling Yang,Changjie Chen
Curcumin (Cur) has been widely used in medicine, due to its antibacterial, anti-inflammatory, antioxidant, and antitumor effects. However, its clinic application is limited by its instability and poor solubility. In the present wok, curcumin was loaded into solid lipid nanoparticles (SLNs), in order to improve the therapeutic efficacy for breast cancer. The results measured using transmission electron microscopy (TEM) indicated that Cur-SLNs have a well-defined spherical shape; the size was about 40 nm with a negative surface charge. The drug loading and encapsulation efficiency in SLNs reached 23.38% and 72.47%, respectively. The Cur-SLNs showed a stronger cytotoxicity against SKBR3 cells. In vitro cellular uptake study demonstrated a high uptake efficiency of the Cur-SLNs by SKBR3 cells. Moreover, Cur-SLNs induced higher apoptosis in SKBR3 cells, compared to cells treated by free drug. In addition, Western blot analysis revealed that Cur-SLNs could promote the ratio ofBax/Bcl-2, but decreased the expression ofcyclin D1andCDK4. These results suggested that Cur-SLNs could be a potential useful chemotherapeutic formulation for breast cancer therapy.Keywords:solid lipid nanoparticle;curcumin;breast cancer;cyclin D1
研究领域:
药学
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肿瘤学
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纳米技术
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DOI
PubMed
高影响因子
JOURNAL OF MEDICINAL CHEMISTRY
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2022
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IF 8.039
Haohao Wang,Di Wu,Chunyu Gao,Hongbo Teng,Yan Zhao,Zhongmei He,Weijia Chen,Ying Zong,Rui Du
In this study, 70 new seco-lupane triterpene derivatives were designed, synthesized, and characterized, and their in vitro anticancer activities were evaluated. Structure–activity relationship studies showed that most compounds inhibited the growth of a variety of tumor cells in vitro. With the extension of alkyl chains, the activity of azole compounds gradually increased while that of indole compounds first increased and then decreased. Moreover, all indole derivatives showed stronger anticancer activity than azole derivatives. In addition, compound 21 showed the strongest inhibitory effect on HepG2 cells with an IC50 value of 0.97 μM. Mechanistic studies showed that compound 21 coregulates the cell death process by inducing ferroptosis and regulating the cell cycle. In conclusion, compound 21 can be used as a ferroptosis inducer and cycle blocker to regulate the HepG2 death process, and it has the potential to become an effective new drug for the treatment of hepatocellular carcinoma.
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DOI
PubMed
高影响因子
MEDICAL SCIENCE MONITOR
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2020
·
IF 1.918
Xiaolin Pu,Hua Jiang,Wei Li,Lin Xu,Lin Wang,Yongqian Shu
Background The coatomer protein complex subunit beta 2 (COPB2) gene is upregulated and promotes cell proliferation in some cancer cells. This study aimed to investigate the role of microRNA (miRNA) targeting by COPB2 gene expression in human lung adenocarcinoma cell lines, including NCI-H1975 cells. Material/Methods COPB2 expression in normal human bronchial epithelial cells and lung adenocarcinoma cells was measured by quantitative reverse transcription-polymerase chain reaction (qRT-PCR) and Western blot. NCI-H1975 human lung adenocarcinoma cells were transfected with short-interfering COPB2 (siCOPB2). Cell apoptosis and cell proliferation were evaluated by flow cytometry and Cell Counting Kit-8 (CCK-8) assays, respectively. The transwell assay evaluated cell migration. Targeting of miR-335-3p by COPB2 was predicted using TargetScan 7.2 and verified using a dual-luciferase reporter assay in NCI-H1975 cells. MiR-335-3p mimics were transfected into NCI-H1975 cells. The further functional analysis included detection of protein expression for cyclin D1, tissue inhibitor matrix metalloproteinase-1 (TIMP-1), matrix metallopeptidase 9 (MMP9), Bcl-2, and Bax, to verify the role of miR-335-3p targeting by COPB2 in lung adenocarcinoma cells. Results COPB2 was upregulated in lung adenocarcinoma cells and was a direct target of miR-335-3p mimics. COPB2 knockdown promoted cell apoptosis, inhibited cell migration and proliferation in NCI-H1975 cells. The effects of COPB2 knockdown on NCI-H1975 cells were increased by miR-335-3p mimics, which also further reduced the expression levels of cyclin D1, MMP9, and Bcl-2 and further increased TIMP-1 and Bax by siCOPB2. Conclusions This study showed that COPB2 was the functional target of miR-335-3p in NCI-H1975 human adenocarcinoma cells.
研究领域:
肿瘤学
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分子生物学
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细胞生物学
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DOI
PubMed
高影响因子
IN VITRO CELLULAR & DEVELOPMENTAL BIOLOGY-ANIMAL
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2022
·Vol. 58
·期 2
·96-108
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IF 2.723
Sun Xiaogang,Hou Zhiyun,Li Ning,Zhang Shuangwei
Hepatocellular carcinoma (HCC) is the most common primary liver cancer with high incidence and mortality. MiR-597-5p is downregulated in tumor tissues of HCC compared with non-tumor tissues. However, its role in HCC is still unknown. This study aims to assess the function of miR-597-5p in HCC development and investigate the underlying mechanism. To perform gain- and loss-of-function studies, SK-HEP-1 cells and Huh-7 cells were transfected with miR-597-5p mimics and inhibitor, respectively. MiR-597-5p markedly reduced the cell viability and the expression of Ki-67 in HCC cells. MiR-597-5p also repressed the cell cycle progression of HCC cells and the protein levels of cyclin D1 and CDK2. Moreover, miR597-5p inhibited the migration and invasion of HCC cells and decreased MMP2 and MMP9 levels. Transcriptional enhancer associate domain transcription factor 1 (TEAD1) was identified as a target of miR-597-5p by luciferase reporter assay. TEAD1 and its downstream target genes, CTGF and CYR61, were downregulated by miR-597-5p in HCC cells. Furthermore, miR-597-5p was demonstrated to function in HCC progression by targeting TEAD1 via TEAD1 expression gain and loss. Our study demonstrates that miR-597-5p represses the proliferation, migration, and invasion of HCC cells through targeting TEAD1, which provides a therapeutic target for HCC treatment.
研究领域:
肿瘤学
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分子生物学
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癌症研究
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DOI
PubMed
高影响因子
Biomaterials Science
·
2017
·Vol. 5
·期 11
·2268-2275
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IF 4.21
Haobo Han,Jiebing Yang,Yudi Wang,Wenqi Chen,Jiawen Chen,Yan Yang,Quanshun Li
The nucleobase analogue 2-amino-6-chloropurine was modified on the surface of polyamidoamine (PAMAM) to construct a derivative AP-PAMAM, and then it was used as a gene carrier for miR-23b delivery to achieve the anti-tumor effects. The carrier AP-PAMAM could condense miR-23b into stable nanoparticles with a particle size of 97.3 nm (N/P ratio of 50), which was favorable for the cellular uptake of nanoparticles. Compared with PAMAM, AP-PAMAM exhibited an obviously enhanced transfection efficiency through the transfection assay of plasmids pEGFP-N3 and pGL-3. Using the human lung adenocarcinoma cell line A549 as a model, AP-PAMAM-mediated miR-23b delivery could achieve a stronger anti-proliferative effect than PAMAM/miR-23b. The inhibition of cell proliferation was elucidated to be associated with the apoptotic induction (apoptotic ratio of 23.2%) and S phase arrest owing to the decreased expression level of cyclin D1. Meanwhile, the AP-PAMAM-mediated miR-23b delivery could suppress the cell migration and invasion of cancer cells through wound healing and Transwell migration assays. In summary, the PAMAM derivative-mediated miR-23b delivery could be a promising strategy for achieving tumor gene therapy.
研究领域:
药学
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分子生物学
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癌症研究
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基因治疗
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DOI
PubMed
高影响因子
ZOOLOGICAL RESEARCH
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2024
·Vol. 45
·期 6
·1287
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IF 4
Yu-Tong Wu,Ze-Qiong Ru,Ying Peng,Zhe Fu,Qiu-Ye Jia,Zi-Jian Kang,Yuan-Sheng Li,Yu-Bing Huang,Sai-Ge Yin,Kun Guo,Nai-Xin Liu,Cheng-An Feng,Jing Tang,Bai-Yu Zhang,Zhi Yang,Ying Wang,Xin-Wang Yang
Individuals with diabetes frequently face serious challenges, including delayed wound healing and increased risk of infection. Notably, the regeneration of hair follicles plays a crucial role in accelerating diabetic skin damage repair, reducing the risk of infection, and enhancing overall skin health. Research has predominantly emphasized the re-epithelialization of diabetic wounds, with a paucity of in-depth studies on hair follicle regeneration. In the current study, we explored the effects of a bioactive amphibian-derived peptide, Cy RL-QN15 , on promoting hair regeneration in a diabetic skin model. In vivo experiments demonstrated that local treatment with Cy RL-QN15 not only accelerated wound healing of scalded skin on the backs of diabetic Kunming (KM) mice but also improved growth of damaged hair follicles. Additionally, back-shaved diabetic C57BL/6 mice showed a significant increase in the growth of newly formed hair after 28 days of continuous Cy RL-QN15 treatment. Further analysis indicated that the hair-regenerating effects of Cy RL-QN15 were closely associated with the proliferation and migration of hair follicle stem cells (HFSCs). Cy RL-QN15 enhanced intracellular β-catenin expression by binding to the Frizzled-7 receptor on the surface of HFSCs. The up-regulation in β-catenin modulated the levels of downstream proteins, such as c-MYC, Cyclin D1, and Lef1, ultimately inducing hair regeneration. This study not only reveals the robust effects of the bioactive peptide Cy RL-QN15 in hair follicle regeneration but also provides novel avenues for the development of more targeted and effective therapeutics for diabetic wound healing in the future.
研究领域:
糖尿病研究
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伤口愈合
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干细胞生物学
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肽疗法
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分子生物学
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DOI
PubMed
高影响因子
Chemical Biology & Drug Design
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2023
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IF 3
Jie Li,Xiuheng Liu
This work is performed to investigate the effect of coptisine (COP) on the malignant biological behaviors of bladder carcinoma cells and its underlying mechanism. Bladder carcinoma cell lines were treated with different concentrations of COP in vitro. Cell counting kit-8 (CCK-8), scratch healing assay, Transwell assay, and flow cytometry were used to detect cell growth, migration, invasion, and cell cycle progression. Bioinformatics analysis was performed to predict the molecular targets of COP. Quantitative real-time PCR and western blot were adopted to determine the expression levels of exportin 1 (XPO1) mRNA and protein, respectively. Gene set enrichment analysis was applied to predict the signaling pathways related to XPO1. This study showed that COP treatment markedly suppressed the malignant biological behaviors of bladder carcinoma cells. XPO1 was identified as a downstream molecular target of COP in bladder carcinoma, and COP treatment inhibited the expression of XPO1 in bladder carcinoma cell lines. Overexpression of XPO1 reversed the impacts of COP on the malignant biological behaviors of bladder carcinoma cells. COP treatment modulated the expression level of cyclin D1 and CYP450 via XPO1. In summary, COP represses the malignant biological behaviors of bladder carcinoma cells and regulates XPO1 expression, which is promising to be a complementary drug for bladder carcinoma treatment.
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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DOI
PubMed
高影响因子
OncoTargets and Therapy
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2023
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IF 4
Gang Wang,Yue Jing,Lingsen Cao,Changchang Gong,Zhunan Gong,Xiangrong Cao
Activation of the transcription factor, signal transducers and activators of transcription 3 (STAT3), has been linked to the proliferation and migration of a variety of human cancer cells. These actions occur via the upregulation or downregulation of cell survival and tumor suppressor genes, respectively. Importantly, agents that can suppress STAT3 activation have the potential for use in the prevention and treatment of various cancers. In this study, an Asiatic acid (AA) derivative, N-(2α,3β,23-acetoxyurs-12-en-28-oyl)-l-proline methyl ester (AA-PMe), is reported to dose dependently suppress constitutive STAT3 activation in gastric cancer cells. This inhibition was mediated by blockade of Janus-activated kinase 2. Additionally, AA-PMe regulated the expression of STAT3-modulated gene products, including cyclin D1, Bax, Bcl-2, c-Myc, and matrix metalloproteinase (MMP)-2 and MMP-9. Finally, transfection with both a STAT3 mimic and an inhibitor reversed the AA-PMe-driven modulation of STAT3 downstream gene products. Overall, these results suggest that AA-PMe is a novel blocker of STAT3 activation and has the potential for the prevention and treatment of gastric cancer.
研究领域:
肿瘤学
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分子生物学
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药理学
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产品关联
DOI
PubMed
高影响因子
International Journal of Peptide Research and Therapeutics
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2020
·Vol. 26
·期 4
·2285-2296
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IF 1.5
Chen Xiaolong,Hu Cuihua,Zhang Yanan,Hao Wenjing,He Xu,Li Qing,Huang Yuxi,Huang Yibing,Chen Yuxin
Conjugation of cell-penetrating peptides to anticancer peptides is an effective strategy to enhance tumor treatment. The hybrid peptide, kla-TAT, by attaching the TAT peptide to the C-terminus of the pro-apoptotic peptide kla exhibited strong anticancer activity when co-administration with other peptide, but the systematic mechanism was not clear. In this study, the mechanisms of action of kla-TAT including the uptake pathway, distribution in cytoplasm, apoptosis-inducing ability and micro-morphology were investigated. The results indicated that the hybrid peptide internalized into A549 cells through two transmembrane mechanisms: endocytosis mediated by the clathrin-mediated endocytosis route and the rapid membrane disruption mechanism. Peptides that were endocytosed could interact with the mitochondrial membrane, while peptides internalized by disrupting the cell membrane caused disruption of the mitochondrial membrane. Thus, the hybrid kla-TAT peptide transfers through the cell membrane, inducing apoptosis by destroying the mitochondrial membrane and causethe expression of cyclin-D1 down-regulation. Meanwhile, the changes of the micro-morphology of the cancer cells was detected using atomic force microscope (AFM) and scanning electron microscope (SEM), which provided the visualized evidence for the mechanism of the peptides.
研究领域:
癌症生物学
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药学
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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
APOPTOSIS
·
2018
·Vol. 23
·期 2
·132-142
·
IF 3.967
Hu Cuihua,Chen Xiaolong,Huang Yibing,Chen Yuxin
In this study, a peptide–peptide co-administration therapy between hybrid peptide kla-TAT and cationic anticancer peptide HPRP-A1 was designed to increase the anticancer activity of the combination peptides through synergistic effect. kla is a pro-apoptotic peptide which could induce rapid cancer cell apoptosis by disruption the mitochondrial membrane when internalized the cells. To enhance more kla peptides pass through cell membrane, a double improvement strategy was designed by chemically conjugation with cell penetration peptide TAT as well as co-administration with cationic membrane active peptide HPRP-A1, and the double anticancer mechanism of the kla-TAT peptide and HPRP-A1 including membrane disruption and apoptosis induction was verified through in vitro experiments. The CompuSyn synergism/antagonism analysis showed that kla-TAT acted synergistically with HPRP-A1 against a non-small cell lung cancer (NSCLC) A549 cell line. The anticancer activities of the two peptides were dramatically increased by co-administration, under the mechanism of cell membrane disruption, caspase-dependent apoptosis induction, as well as cyclin-D1 down-regulation based G1 phase arrest. We believe that the synergic therapeutic strategy would be a meaningful method for the anticancer peptides used in cancer treatment.
研究领域:
肿瘤学
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药学
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细胞生物学
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产品关联
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）