JOURNAL OF GENE MEDICINE
·
2017
·Vol. 19
·期 12
·e2998
·
IF 2.524
Yunna Chen,Li Sun,Dongdong Guo,Ziteng Wu,Weidong Chen
Background Drug resistance cancer cells have become a major problem in chemotherapy. To solve this problem, the co-delivery of small interefering RNA (siRNA) and 5-fluorouracil chitosan nanoparticles was employed, aiming to reverse the multidrug resistance of gastric cancer SGC-7901 cells in vitro . Methods Chitosan nanoparticles were prepared using an ionic gel method. siRNA nanoparticles were characterized by gel retardation assays. Particle size and zeta potential were measured to confirm nanoparticle formation. The transfection efficiency of siRNA was determined by flow cytometry and high-content screening. Western blotting and a quantitative real-time-polymerase chain reaction were used to assess the silencing efficiency of siRNA. Accumulation and efflux experiments for rhodamine-123, cell migration experiments, cell sensitivity analyses and cell apoptosis assays were used to determine whether siRNA could reverse multidrug resistance. A systemic toxicity assay was used to evaluate the safety of nanoparticles. Results Compared to naked siRNA, the co-delivery system demonstrated a higher transfection efficiency and gene silencing efficiency by inhibiting the efflux of P-glycoprotein and cell migration. Moreover, the combination treatment with siRNA and 5-fluorouracil co-delivered by chitosan nanoparticles can increase the sensitivity of drug resistance cells and cell apoptosis. Finally, the safety of nanoparticles was evaluated in vivo and the results obtained suggested that nanoparticles did not have any obvious toxicity. Conclusions Co-delivery of siRNA and 5-fluorouracil chitosan nanoparticles is an attractive strategy for overcoming multidrug resistance.
研究领域:
肿瘤学
·
药学
·
分子生物学
·
纳米技术
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF ETHNOPHARMACOLOGY
·
2018
·
IF 3.115
Hongqing Xie,Xiaotong Li,Yajie Chen,Mingzi Lang,Zhangfei Shen,Liangen Shi
Ethnopharmacological relevance Cordyceps cicadae (Miq.) Massee is a traditional Chinese medicine that has been used for approximately 1600 years in China. C. cicadae , a member of the Cordyceps genus, exerts a therapeutic effect on many diseases, such as cancer. Objective This study aimed to evaluate the antineoplasmic activity of C. cicadae and to identify its molecular mechanism of cell death. Materials and methods The toxicity of the ethanolic extract of C. cicadae (EEC) against different cancer cell lines was determined through MTT assay. Human gastric cancer SGC-7901 cells were treated with EEC for 48 h. Cell morphology was examined by using an Olympus phase-contrast microscope. The cell apoptosis was quantified through Annexin V-FITC/PI staining. Cells were stained with PI and then subjected to flow cytometry for the investigation of cell cycle status. Cells were subjected to mitochondrial membrane potential (MMP) assay after incubation with JC-1 probes and to intracellular Ca 2+ measurement through flow cytometry after incubation with Fluo-3 AM fluorescent probes . Western blot analysis was conducted to quantify the expression of proteins related to apoptosis, cell cycle and endoplasmic reticulum stress. High-performance liquid chromatography (HPLC) analysis was performed to analyse the biological activity components of EEC. Results EEC suppressed the proliferation of SGC-7901 cells and induced the development of abnormal morphological features in a dose-dependent manner. Flow cytometry results indicated that EEC treatment caused cell apoptosis and arrested the cell cycle in the S phase. In addition, EEC treatment triggered MMP depolarization and Ca 2+ overloading in the cytosol of SGC-7901 cells. Western blot analysis demonstrated that EEC increased Bax, AIF, caspase-8, caspase-6 and caspase-3 activities and decreased Bcl-2 activity. The release of cytochrome c from mitochondria was associated with mitochondrial dysfunction, which was caused by the activation of the cell surface receptor Fas and the cleavage of PARP . EEC-induced S phase arrest was associated with the up-regulation of E2F1, cyclin A2 , cyclin E and p53 expression levels and the down-regulation of CDK2 expression. In addition, EEC increased the expression of endoplasmic reticulum stress-related proteins, such as calpain-1, caspase-12 and caspase-9. HPLC assay results suggested that EEC contained adenine , uridine , adenosine and N6-(2-Hydroxyethyl)-adenosine. Conclusion EEC inhibited the proliferation of SGC-7901 cells by inducing caspase-dependent apoptosis, arresting the cell cycle in the S phase and increasing endoplasmic reticulum stress. This study revealed that C. cicadae is a potential natural source of anticancer drugs .
研究领域:
药理学
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肿瘤学
·
传统中药
·
细胞生物学
·
生物化学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Materials Today Communications
·
2024
·
IF 3.7
Yao Yue,Peng Deng,Zhou Wang,Chen Ling,Ziye Zhu,Yongjin Li,Xiajun Zhang
Currently, ferrite magnetic nanoparticles are widely utilized in the biomedical domain, encompassing antibacterial, catalytic, imaging, and drug delivery among other fields. In this study, Cu 0.5 Zn 0.5 Fe 2 O 4 nanoparticles were synthesized via the rapid combustion-calcination process. By incorporating inorganic metal elements with specific functionalities, the limitations of iron oxide could be overcome, enabling targeted roles in various applications. The morphology, phase composition, and magnetic properties were characterized using scanning electron microscopy (SEM), X-ray diffraction (XRD), and vibrating sample magnetometry (VSM). The impact of anhydrous ethanol quantity, calcination temperature, and duration on the magnetic properties and grain size of the nanomaterials was investigated. Cu 0.5 Zn 0.5 Fe 2 O 4 nanoparticles were evaluated for their inhibitory effects on human gastric cancer cells (SGC-7901 and HGC-27) under different preparation conditions. The results of the MTT assay revealed a concentration - and time-dependent inhibition of tumor cell proliferation by Cu 0.5 Zn 0.5 Fe 2 O 4 nanoparticles. Nanoparticles exhibiting a magnetic energy of 20.23 emu/g and an average particle size of 51.6 nm, synthesized using 20 mL of anhydrous ethanol, calcination temperature of 400 °C, and a calcination duration of 2.0 h, displayed significant inhibitory effects on tumor cells. Furthermore, The nanoparticles not only showed low toxicity to human normal stomach cells GES-1, but also enhanced the inhibitory effect on tumor cells under the action of an external magnetic field.
研究领域:
纳米技术
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生物医学工程
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材料科学
·
肿瘤学
✓ 已验证
产品关联
DOI
高影响因子
INVESTIGATIONAL NEW DRUGS
·
2020
·Vol. 39
·期 3
·627-635
·
IF 3.525
Chu Yafei,Xiao Zheng,Jing Nan,Yan Wenjuan,Wang Shanmei,Ma Bing,Zhang Jiangfeng,Li Yi
Arborinine is a natural product isolated from G. parva leaf extracts, which displays potentially antiproliferative activity against human cervical cancer cells. In contrast, its anticancer effects against gastric cancer cells and drug-resistant gastric cancer cells remain unknown. In this work, arborinine was evaluated as a broad-spectrum antiproliferative agent, and it exhibited potently inhibitory activity against NCI-N87 (IC 50 = 5.67 μM), BGC-823 (IC 50 = 7.26 μM), MGC803 (IC 50 = 4.75 μM), SGC-7901 (IC 50 = 1.96 μM), HGC-27 (IC 50 = 5.70 μM), SGC-7901/ADR (IC 50 = 0.24 μM), SGC-7901/VCR (IC 50 = 1.09 μM), and MGC803/PTX (IC 50 = 1.32 μM) cell lines. Subsequent target verification experiments demonstrated that arborinine selectively and reversibly inhibited LSD1 in a time-dependent manner. Furthermore, it was found that arborinine suppressed the epithelial-mesenchymal transition of gastric cancer cell line SGC-7901 and adriamycin-resistant gastric cancer cell line SGC-7901/ADR in a dose-dependent manner. The in vivo antitumor study further indicated that arborinine can significantly reduce the growth of tumors both in SGC-7901 and SGC-7901/ADR xenograft mouse models. Overall, we demonstrated the potential of arborinine as an effective treatment for gastric cancer and adriamycin-resistant gastric cancer.
研究领域:
肿瘤学
·
药理学
·
细胞生物学
✓ 已验证
DOI
PubMed
高影响因子
Theranostics
·
2021
·
IF 11.556
Yiqun Xia,Jundixia Chen,Yun Yu,Fengjiao Wu,Xin Shen,Chenyu Qiu,Tingting Zhang,Lin Hong,Peisen Zheng,Rongrong Shao,Chenxin Xu,Fang Wu,Wei Chen,Congying Xie,Ri Cui,Peng Zou
Background: Cancer is a leading cause of death worldwide. Extensive research over decades has led to the development of therapies that inhibit oncogenic signaling pathways. The mammalian target of rapamycin (mTOR) signaling pathway plays an important role in the development of many cancers. Several mTOR inhibitors are approved for the treatment of cancers. However, the anticancer efficacies of mTOR inhibitor monotherapy are still limited. Methods: Western blot was used to detect the expression of indicated molecules. Thioredoxin reductase (TrxR) activity in cells was determined by the endpoint insulin reduction assay. Immunofluorescence staining was used to analyze precise location and expression of target proteins. Nude mice were used for xenograft tumor models. Results: We identified a synergistic lethal interaction of mTOR and TrxR inhibitors and elucidated the underlying molecular mechanisms of this synergism. We demonstrated that mTOR and TrxR inhibitors cooperated to induce cell death by triggering oxidative stress, which led to activation of autophagy, endoplasmic reticulum (ER) stress and c-Jun N-terminal Kinase (JNK) signaling pathway in cancer cells. Remarkably, we found that auranofin (AF) combined with everolimus significantly suppressed tumor growth in HCT116 and SGC-7901 xenograft models with no significant signs of toxicity. Conclusion: Our findings identify a promising therapeutic combination for cancer and has important implications for developing mTOR inhibitor-based combination treatments.
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
JOURNAL OF ASIAN NATURAL PRODUCTS RESEARCH
·
2014
·
IF 0.968
Ping Guo,Yue-Wu Wang,Bi-Xia Weng,Xiao-Kun Li,Shu-Lin Yang,Fa-Qing Ye
Using curcumol that was extracted from the volatile oil of Rhizoma Curcumae as the raw material, its derivatives were synthesized and purified. The structures of these compounds were confirmed by 1H, 13C NMR, and mass spectral data. The test compounds were evaluated for their in vitro anti-tumor activity against gastric cancer cell lines SGC-7901 and lung carcinoma cell line H460 by methyl thiazolyl tetrazolium chromatometry. Distinct structure–activity relationships of these curcumol derivatives were also revealed for inhibiting cell proliferation. Presence of electron-withdrawing groups or amino could increase the activity significantly, whereas esterification of 8-hydroxy diminished the anti-tumor activity. Many of the tested candidates exhibited higher inhibition efficiency than curcumol, suggesting that structural modifications could enhance its activity effectively.
研究领域:
药理学
·
化学
·
肿瘤学
✓ 已验证
DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF MOLECULAR MEDICINE
·
2018
·Vol. 42
·期 3
·1473-1483
·
IF 2.784
Jun Fu,Luhua Yu,Jie Luo,Rui Huo,Bing Zhu
The purpose of the present study was to analyze the association between paeonol and the known genes related to gastric cancer (GC) using bioinformatics methods, and to investigate the role of paeonol in the potential impact on the nuclear factor‑κB (NF‑κB) signaling pathway, in order to provide a theoretical basis for further elucidating the effect of paeonol on cancer cells. Cell viability, morphology and apoptosis were detected using an MTT assay, an inverted microscope, and flow cytometry, respectively. The correlation between drugs and genes was analyzed using the Search Tool for Interactions of Chemicals (STITCH) gene‑drug interaction network. The expression levels of related mRNA and proteins were determined using reverse transcription‑quantitative polymerase chain reaction analysis and enzyme‑linked immunosorbent assay. The changes in protein expression were examined using western blot analysis. The correlation network between target genes directly affected by paeonol and known GC genes was determined by analyzing the association between the compounds and genes recorded in the STITCH database. The GC‑related epidermal growth factor receptor 2 (ERBB2) gene was at the core position of the paeonol interaction network and may be an important potential target gene for the effect of paeonol on cancer cells. The effect of paeonol on the viability of the SGC‑7901 GC cell line was detected using an MTT assay, which showed that the inhibitory effect occurred in a time‑ and dose‑dependent manner. The observations of cell morphology demonstrated that the cells were floating, abnormal in shape, had unclear boundaries and were sparse in arrangement following paeonol treatment. Flow cytometry indicated that paeonol significantly accelerated the apoptotic rate of the SGC‑7901 GC cells. The examination of clinical samples suggested that ERBB2 was expressed at a high level in GC samples, and was significantly downregulated following the addition of paeonol. The western blot analysis revealed that downregulating ERBB2 affected the activation of the NF‑κB signaling pathway, thereby upregulating the pro‑apoptotic factor B‑cell lymphoma‑associated X protein. Taken together, paeonol significantly downregulated ERBB2 and inhibited the activation of the NF‑κB signaling pathway, thereby inhibiting the proliferation of SGC‑7901 cells and inducing apoptosis.
研究领域:
肿瘤学
·
药理学
·
分子生物学
·
生物信息学
✓ 已验证
DOI
PubMed
高影响因子
Arabian Journal of Chemistry
·
2023
·
IF 6
Mingyi Ma,Zhixiang Lv,You Li,Ziye Zhu,Chen Ling,Dawei He,Ruijiang Liu
Problem Unhealthy dietary habits and inadequate existing treatment technologies have led to high morbidity and mortality rates in patients with gastric cancer, and the research shows that curcumin has excellent antitumor properties, however, the non-water-soluble characteristic of curcumin limits its applications. To break the limitation, the targeted drug carriers become the urgent need to treat gastric cancer. Method The heterogeneous magnetic α-Fe 2 O 3 /Fe 3 O 4 nanoparticles were obtained by rapid combustion method with citric acid (CA) and ferric nitrate as raw materials and anhydrous ethanol as solvent and fuel, and then modified with citric acid (CA) and chitosan (CTS), and loaded curcumin (Cur) to form α-Fe 2 O 3 /Fe 3 O 4 -CA-CTS-Cur nanosystem. Results The particle sizes of heterogeneous magnetic α-Fe 2 O 3 /Fe 3 O 4 nanoparticles and α-Fe 2 O 3 /Fe 3 O 4 -CA-CTS-Cur nanosystem were 24.9 nm and 35.6 nm, respectively, and their respective saturation magnetization were 70.9 emu/g and 30.3 emu/g. The magnetic α-Fe 2 O 3 /Fe 3 O 4 -CA-CTS-Cur nanosystem had good stability, excellent drug release rate, and enhanced apoptosis to gastric cancer cells (SGC-7901) through the caspase pathway and ferroptosis of cells. Conclusions The magnetic drug delivery nanosystem was successfully constructed, and revealed significant inhibitory and killing effects on SGC-7901 cells, and low toxic and side effects on normal cells.
研究领域:
肿瘤学
·
纳米医学
·
药理学
✓ 已验证
产品关联
DOI
高影响因子
ANTI-CANCER DRUGS
·
2019
·Vol. 30
·期 1
·46-55
·
IF 1.801
Lin Fuxing,Yang Jie,Muhammad Umair,Sun Jing,Huang Zhenghua,Li Wei,Lv Fengxia,Lu Zhaoxin
Bacillomycin D can inhibit the growth of Aspergillus ochraceus in food samples. In addition, it can induce apoptosis in and inhibit the proliferation of cancer cells, although the details of this mechanism are unknown. In this study, we separated bacillomycin D-C14, D-C15, D-C16
monomers from the Bacillus subtilis strain fmbJ. The bacillomycin D monomers containing longer fatty acid chains better induced apoptosis in Bgc-823, Sgc-7901, and Hgc-27 gastric cancer cells. The Bgc-823 cell line was the most sensitive. Acridine orange-ethidium bromide staining indicated
that bacillomycin D-C16-induced Bgc-823 cell death by triggering apoptosis, characterized by membrane blebbing, cellular shrinkage, and DNA fragmentation. Flow cytometric analysis showed a bacillomycin D-C16 dose-dependent trigger of Bgc-823 apoptosis. Bacillomycin D-C16-induced the mitochondrial
pathway, as indicated by a reduced Bcl-2/Bax expression ratio, enhanced cytochrome C release, and higher levels of cleaved caspase-3. Furthermore, bacillomycin D-C16 effectively repressed phosphorylation of the serine–threonine protein kinase Akt at Ser-473 and increased the levels of
the FoxO3a protein. The combination of the PI3K/Akt-inhibitor BEZ235 with bacillomycin D-C16 enhanced the apoptosis of Bgc-823 cells. Together, these findings indicated that bacillomycin D-C16 induces apoptosis through the PI3K/Akt and FoxO3a signaling pathways.
研究领域:
肿瘤学
·
分子生物学
·
细胞生物学
·
药理学
✓ 已验证
DOI
PubMed
高影响因子
BIOMEDICINE & PHARMACOTHERAPY
·
2017
·
IF 2.759
Yanyan Zhu,Yameng Jiang,Lei Shi,Linying Du,Xiaodong Xu,Enxia Wang,Yong Sun,Xin Guo,Boyang Zou,Huaxin Wang,Changyuan Wang,Lidan Sun,Yuhong Zhen
7- O -Geranylquercetin (GQ) is a novel O -alkylated derivate of quercetin . In this study, we evaluated its apoptosis induction effects in human gastric cancer cell lines SGC-7901 and MGC-803 and explored the potential molecular mechanisms. The results demonstrated that GQ lowered viability of SGC-7901 and MGC-803 cells in a dose- and time-dependent manner without apparent cytotoxicity to human gastric epithelial cell line GES-1. GQ could induce apoptosis in SGC-7901 and MGC-803cells, and arrest the gastric cancer cells at G2/M phase. Mechanism study showed that GQ triggered generation of reactive oxygen species (ROS), then activated p38 and JNK signaling pathways , subsequently led to mitochondrial impairment by regulating the expression of Bcl-2, Bcl-xl and Bax, and finally promoted the release of cytochrome c and the activation of caspases to induce apoptosis. In addition, Z-VAD-FMK (caspase inhibitor) could reverse GQ-induced apoptosis. SB203580 (p38 inhibitor) and SP600125 (JNK inhibitor) could rescue GQ-induced cell death and attenuate mitochondrial signal pathway activation. Furthermore, NAC (ROS inhibitor) could rescue GQ-induced cell death, reduce ROS generation, decrease the phosphorylation of p38 and JNK, and then attenuate the activation of mitochondrial signal pathway. Taken together, GQ induces caspase-dependent apoptosis in gastric cancer cells through activating ROS-MAPK mediated mitochondrial signal pathway. This study highlights the potential use of GQ as a gastric cancer therapeutic agent.
研究领域:
肿瘤学
·
药理学
·
细胞生物学
·
分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Drug Design Development and Therapy
·
2017
·
IF 2.822
Jingrun Chen,Junjie Liu,Dongxiao Cui,Chaoqun Yan,Liqiang Meng,Liqian Sun,Shurong Ban,Rui Ge,Taigang Liang,Qingshan Li
This study deals with the design and synthesis of a series of novel 4-methoxy-substituted and 5-methyl-substituted (3′S,4′S)-(−)-cis-khellactones. The newly synthesized compounds were characterized by 1H nuclear magnetic resonance (NMR), 13C-NMR, mass spectrometry, and elemental analysis. All the derivatives were subjected to in vitro cytotoxicity screening against HEPG-2 (human liver carcinoma), SGC-7901 (human gastric carcinoma), and LS174T (human colon carcinoma), by using the MTT assay. The results revealed that several of the 4-methoxy-substituted compounds exhibited potent cytotoxicity. Among these, compound 12e showed the highest activity against cancer cells which 50% inhibitory concentration (IC50) values were in the range of 6.1–9.2 μM with low toxicity on normal human hepatocyte. Preliminary investigation of possible mechanisms of action of compound 12e against HEPG-2 cells indicated possible induction of apoptosis, as determined by morphological observations and Annexin V/propidium iodide (PI) double staining, in addition to apparent dissipation of mitochondrial membrane potential (MMP), as measured by 5,5′,6,6′-tetrachloro-1,1′,3,3′-tetraethyl-imidacarbocyanine iodide (JC-1) staining in combination with the activation of caspase-9 and caspase-3 by Western blot analysis. Overall, the data suggest that compound 12e may be a promising potential anti-cancer agent that could act primarily by inducing apoptosis through the mitochondria-mediated intrinsic pathway in human hepatoma cells.
研究领域:
药理学
·
肿瘤学
·
药物化学
✓ 已验证
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）