FOOD AND CHEMICAL TOXICOLOGY
·
2025
·
IF 3.5
Min Li,Shuaijun Peng,Jingjing Bu,Siqi Quan,Liming Liu,Zhouli Yue,Linlin Wang,Yucheng Li
Gefitinib, a first-line tyrosine kinase inhibitor (TKI) target to non-small cell lung cancer (NSCLC) treatment, is known to cause hepatotoxicity, which seriously limiting its therapeutic application. This study investigated the underlying mechanisms of gefitinib-induced liver injury and the protective effects of glycyrrhizic acid (GL) in mice and AML12 cells. Sixty mice were randomly divided into six groups: control, gefitinib, glutathione (200 mg/kg), and three doses of GL (50, 100, and 200 mg/kg). Liver injury was induced in mice through daily oral administration of gefitinib (400 mg/kg) for 16 days, with hepatotoxicity was assessed through serum alanine transaminase (ALT) and aspartate transaminase (AST) levels, and hepatic histopathology. Hepatic mRNA profiles were analyzed using RNA sequencing, with differentially expressed genes (DEGs) confirmed by reverse transcription quantitative polymerase chain reaction (RT-qPCR) and Western blot. Finally, the effect of GL on the anticancer efficacy of gefitinib was assessed in A549 and Lewis lung carcinoma (LLC) lung cancer cells, as well as in a urethane-induced lung cancer mouse model. GL treatment significantly reduced liver index and serum ALT and AST levels, while also improving hepatic histopathology. Transcriptomic analysis identified 114 DEGs linked to the p53 pathway and cell cycle regulation. Further study indicated that GL inhibited the expression of p53 and p21, thereby upregulated Cyclin D1 expression, thereby alleviating gefitinib-induced cell cycle arrest without impairing its anticancer activity in vivo and in vitro . These findings highlight the potential of GL as a safe adjunct therapy, effectively mitigating gefitinib-induced hepatotoxicity while preserving its anticancer efficacy.
研究领域:
药理学
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肿瘤学
·
分子生物学
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产品关联
DOI
PubMed
高影响因子
CELL CYCLE
·
2020
·
IF 3.699
Yanjie Hu,Jisong Zhang,Huihui Hu,Shan Xu,Li Xu,Enguo Chen
Gefitinib (GEB) is one of the drugs used for patients with epidermal growth factor receptor (EGFR)-positive mutations in non-small cell lung cancer (NSCLC). However, application of GEB is limited by its low water solubility, stability, and utilization rate, especially the side effects while GEB is given by oral. In this study, nanoliposome was used as a carrier to prepare nanoliposome compound drug (GL) by embedding GEB in the nanoliposome perfectly combined with green nontoxic solvent and thin-film dispersion method. The nanoliposome structure was expected to improve the water solubility and biocompatibility of GEB, thus improving the effect of cancer treatment. The surface electronegative nanoliposomes can effectively avoid protein adsorption and prolong the circulation time in vivo. Meanwhile, the ratio of lecithin to cholesterol (LE/CH) was explored to maximize the encapsulation efficiency of nanoliposome. Subsequent test results showed that GL exhibited better stability, smaller particle size and higher encapsulation efficiency. In addition, in vitro drug release curve also further confirmed that GL had a promising drug sustained-release effect. In particular, a series of in vitro tests such as cell activity, apoptosis, colony formation, scratch, invasion, and cell cycle assays were performed. The results indicated that GL significantly enhanced the pro-apoptotic effect on A549 cells. Most cell cycles of A549 cells were blocked in the G0/G1 phase influenced by GL, thus inhibiting the proliferation of cancer cells. In vivo anti-tumor studies showed that compared with pure GEB, GL had a significant inhibiting effect on NSCLC. In conclusion, the GL which was synthesized by a simple method in this study significantly improved the treatment effect of cancer cells, which proved that the nanoliposome carrier had an excellent application prospect in the treatment of lung cancer.
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
Cancer Communications
·
2018
·Vol. 38
·期 1
·1-14
·
IF 0
Huang Yanjun,Zhou Sichun,He Caimei,Deng Jun,Tao Ting,Su Qiongli,Darko Kwame Oteng,Peng Mei,Yang Xiaoping
Background In previous studies, we have shown that the combination of metformin and gefitinib inhibits the growth of bladder cancer cells. Here we examined whether the metformin analogue phenformin, either used alone or in combination with gefitinib, could inhibit growth of bladder cancer cells.Methods The growth-inhibitory effects of phenformin and gefitinib were tested in one murine and two human bladder cancer cell lines using MTT and clonogenic assays. Effects on cell migration were assessed in a wound healing assay. Synergistic action between the two drugs was assessed using CompuSyn software. The potential involvement of AMPK and EGFR pathways in the effects of phenformin and gefitinib was explored using Western blotting.Results In MTT and clonogenic assays, phenformin was > 10-fold more potent than metformin in inhibiting bladder cancer cell growth. Phenformin also potently inhibited cell migration in wound healing assays, and promoted apoptosis. AMPK signaling was activated; EGFR signaling was inhibited. Phenformin was synergistic with gefitinib, with the combination of drugs showing much stronger anticancer activity and apoptotic activation than phenformin alone.Conclusion sPhenformin shows potential as an effective drug against bladder cancer, either alone or in combination with gefitinib.
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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产品关联
DOI
PubMed
JOURNAL OF PHOTOCHEMISTRY AND PHOTOBIOLOGY B-BIOLOGY
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2015
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IF 2.96
Jie-Hua Shi,Ting-Ting Liu,Min Jiang,Jun Chen,Qi Wang
The binding interaction of gefitinib with calf thymus DNA (ct-DNA) under the simulated physiological pH condition was studied employing UV absorption, fluorescence, circular dichroism (CD), viscosity measurement and molecular docking methods. The experimental results revealed that gefitinib preferred to bind to the minor groove of ct-DNA with the binding constant ( K b ) of 1.29 × 10 4 L mol −1 at 298 K. Base on the signs and magnitudes of the enthalpy change (Δ H 0 = −60.4 kJ mol −1 ) and entropy change (Δ S 0 = −124.7 J mol −1 K −1 ) in the binding process and the results of molecular docking, it can be concluded that the main interaction forces between gefitinib and ct-DNA in the binding process were van der Waals force and hydrogen bonding interaction. The results of CD experiments revealed that gefitinib did not disturb native B-conformation of ct-DNA. And, the significant change in the conformation of gefitinib in gefitinib–ct-DNA complex was observed from the molecular docking results and the change was close relation with the structure of B-DNA fragments, indicating that the flexibility of gefitinib molecule also plays an important role in the formation of the stable gefitinib–ct-DNA complex.
研究领域:
生物化学
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药物化学
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分子生物学
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产品关联
DOI
PubMed
高影响因子
RSC Advances
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2018
·Vol. 8
·期 4
·2082-2091
·
IF 2.936
Yangui Chen,Xiaoxia Li,Hong Xiao,Jinpeng Xiao,Bo Li,Xiaoyan Chen,Yong Wang,Du Cheng,Xintao Shuai
Owing to the complexity of tumorgenesis, combination therapy has proven to be a viable strategy for cancer treatment in recent years. However, the delivery and site-specific release of different therapeutic agents remain a major challenge in combination therapy. In this study, a polymeric nanovesicle based on a copolymer of polyethylene glycol and a polypeptide derivative was introduced as a vector to simultaneously deliver hydrophobic gefitinib and hydrophilic doxorubicin hydrochloride for multi-target combination therapy. The vesicle incorporating the two drugs exhibited prominent pH/reduction sensitivities to trigger the release of gefitinib and doxorubicin inside cancer cells. The two drugs co-delivered by the polymeric nanovesicle exhibited a joint anticancer effect both in vitro and in vivo. In particular, a remarkable therapeutic effect was demonstrated in animal studies using a mouse N2a neuroblastoma model. This study reveals the potential of reduction and pH dual-responsive nanovesicles bearing gefitinib and doxorubicin as an effective nano-medicine for cancer treatment.
研究领域:
药学科学
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癌症研究
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纳米技术
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药物递送系统
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF MATERIALS SCIENCE
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2018
·Vol. 53
·期 21
·14907-14921
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IF 2.993
Pang Jiafeng,Li Zhixian,Li Shaomin,Lin Shuying,Wang Hongdi,Xie Qiuling,Jiang Yanbin
Integrating various functional components into a single nano-platform is an ideal but challenging strategy for cancer therapy. Herein, a facile approach to fabricating multi-targeted nano-drug delivery systems which can be monitored is reported. Superparamagnetic iron oxide nanoparticles (SPIONs) and gefitinib (GEF) were encapsulated into folic acid-conjugated zein (Fa–zein) nanocomplexes (GEF-FSZs) with good dispersity, high GEF loading efficiency and pH-dependent release profile. The uptake of water-insoluble GEF was facilitated by encapsulating GEF into a zein-based nanocomplex, the magnetic responsive property endowed by SPIONs and the conjugation of Fa, which resulted in enhanced toxicity to A549 cells. The endocytosis study indicated that macropinocytosis and clathrin/caveolae-independent endocytosis exerted great influence on the internalization of GEF-FSZs. These results implied that GEF-FSZs could be a promising candidate for controlled and targeted drug delivery.
研究领域:
纳米技术
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药学
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癌症治疗
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材料科学
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生物医学工程
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产品关联
DOI
高影响因子
Scientific Reports
·
2016
·Vol. 6
·期 1
·1-10
·
IF 5.228
Peng Mei,Huang Yanjun,Tao Ting,Peng Cai-Yun,Su Qiongli,Xu Wanjun,Darko Kwame Oteng,Tao Xiaojun,Yang Xiaoping
EGFR is a potential therapeutic target for treating bladder cancer, but has not been approved for clinical use yet. Metformin is a widely used antidiabetic drug and has demonstrated interesting anticancer effects on various cancer models, alone or in combination with chemotherapeutic drugs. The efficacy of gefitinib, a well-known EGFR tyrosine kinase inhibitor, combined with metformin was assessed on bladder cancer and underlying mechanisms were explored. This drug combination induced a strong anti-proliferative and anti-colony forming effect and apoptosis in bladder cancer cell lines. Gefitinib suppressed EGFR signaling and inhibited phosphorylation of ERK and Akt. Metformin amplified this inhibitory effect and enhanced gefitinib-induced activation of AMPK signaling pathway. In vivo intravesical treatment of metformin and gefitinib on syngeneic orthotopic mice confirmed the significant inhibitory effect on bladder tumor growth. These two drugs may be an excellent combination for the treatment of bladder cancer through intravesical instillation.
研究领域:
肿瘤学
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药理学
·
分子生物学
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产品关联
DOI
PubMed
高影响因子
DRUG DEVELOPMENT RESEARCH
·
2023
·Vol. 84
·期 3
·582-600
·
IF 3.8
Jiabin Zhou,Yuhan Liu,Jun Chen,Nanxiang Xiong,Dongye Yi
Kaempferol (Kae) is a natural flavonoid that has multiple biological activities, such as anti-inflammatory and antitumor activities. However, few studies have been reported on antiglioma effects of Kae. This study aimed to explore the effects and potential mechanisms of Kae and synergistic antitumor activities with gefitinib (Gef) on glioma. Cell Counting Kit-8 and 5-ethynyl-2'-deoxyuridine assays were used to detect cytotoxicity and cell proliferation. Cell apoptosis and the cell cycle were detected by flow cytometry. Transwell assays were used to detect the migratory and invasive abilities of glioma cells. Network pharmacology and molecular docking analysis were used to screen for core targets of Kae in glioma therapy. Xenograft tumor nude mice were established with U251 cells to verify the antiglioma effects of Kae in vivo. A terminal deoxynucleotidyl transferase dUTP nick end labeling assay was used to detect apoptosis in tumor tissues. The expression of proteins was detected by immunohistochemistry and western blot analysis. Kae inhibited cell proliferation, promoted apoptosis, and induced cell cycle arrest in the G2/M phase of glioma cells in a concentration-dependent manner. Kae inhibited the migration and invasion of glioma cells at low concentrations. Network pharmacology analyses showed that epidermal growth factor receptor (EGFR) and SRC proto-oncogene (SRC) might be direct molecular-binding targets of Kae. Our results showed that Kae inhibited the levels of phosphorylated EGFR, phosphorylated SRC (p-SRC), and phosphorylated signal transducer and activator of transcription 3 (STAT3). In addition, the combination of Kae with Gef significantly inhibited the proliferation of glioma cells. Kae further inhibited EGFR phosphorylation after treatment with Gef. Similarly, Kae further enhanced the inhibition of p-SRC caused by SU6656. Finally, we demonstrated that Kae exerted great antitumor activities and enhanced the antitumor effect of Gef by inhibiting EGFR/SRC/STAT3 signaling pathway in vivo. Kae played a potential role and synergistic antiglioma effects with Gef by inhibiting the phosphorylation of EGFR/SRC dual targets. Kae is expected to be a candidate drug or chemosensitizer in glioma therapy.
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
LUMINESCENCE
·
2026
·Vol. 41
·期 2
·e70439
·
IF 2.8
Yuxun Zhao,Qiuhua Wu,Lu Bai,Chenghuan Wang,Guolin Zhang,Wenxiao Yang
Blue fluorescent carbon dots (CDs) were synthesized in this study from poly (butylene adipate co -terephthalate) (PBAT) and poly (ethylene terephthalate) (PET) waste through a sequential carbonization and hydrothermal treatment. The nanoparticles exhibited a spherical morphology with a narrow size distribution of 1.3–2.5 nm, abundant hydrophilic surface groups, and excellent dispersibility in aqueous solution. The CDs exhibited strong blue fluorescence with a quantum yield (QY) of 7.4% and remarkable stability. The fluorescence was selectively quenched by gefitinib primarily via a Förster resonance energy transfer (FRET) mechanism. The developed sensor showed a linear detection range of 0–30 μM, a low detection limit of 0.8433 μM, and outstanding anti-interference capability against common biomolecules and structurally similar drugs. The spiked recovery rates in real samples ranged from 96.7% to 103.0%, with the relative standard deviations (RSDs) less than 3.0%, demonstrating the probe's capability for detecting gefitinib in complex practical matrices. The proposed sensor shows great potential for applications in therapeutic drug monitoring and clinical diagnostics, offering a promising solution for both environmental sustainability and analytical science.
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产品关联
DOI
PubMed
高影响因子
PHYTOMEDICINE
·
2025
·
IF 8.3
Min Jiang,Chao Hong,Wenkui Zou,Zheng Ye,Kexu Gu,Yaning Ren,MingFang Li,Don Green,Tong Zhang,Yue Ding
Background Drug resistance severely hinders the clinical application of epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) in the treatment of non-small cell lung cancer (NSCLC). Notably, resistance caused by rare target mutations (with a mutation incidence rate below 5%) accounts for approximately 15% of total resistance cases in NSCLC. Due to the diversity and complexity of these mutations, targeted therapies against them are currently very limited. Purpose To address the challenge of multi-driver resistance in NSCLC, this study aimed to explore a novel therapeutic strategy that can simultaneously inhibit multiple resistance drivers and enhance drug resensitization to EGFR-TKIs, overcoming the limitations of conventional single-protein inhibitors. Methods Established gefitinib-resistant HCC827 cell models driven by rare co-activation of two EGFR-independent membrane proteins. Developed a strategy targeting lipid raft cholesterol to destabilize raft integrity, leveraging the cholesterol-modulating properties of ginsenosides. Evaluated the synergistic effect of co-administering ginsenoside Rg3 with gefitinib in both in vitro and in vivo models. Explored the mechanism of Rg3 action, including its binding to lipid raft cholesterol, disruption of membrane anchoring of resistance-associated receptor tyrosine kinases, and acceleration of their endocytic degradation. Results : Co-administration of ginsenoside Rg3 with gefitinib synergistically restored antitumor efficacy in both in vitro and in vivo models, outperforming conventional single-protein inhibitors. Mechanistically, Rg3 specifically binds to lipid raft cholesterol, disrupting the membrane anchoring of resistance-associated receptor tyrosine kinases (e.g., FGFR1 and VEGFR2) and accelerating their endocytic degradation. Structural-activity relationship analyses revealed that the cholesterol-binding capacity of ginsenosides—critical for resistance reversal—is modulated by the stereochemical configuration of sugar moieties at C3, C6, and C20 positions. Conclusions This study elucidates a novel membrane-centric paradigm for overcoming multi-driver resistance in NSCLC, where pharmacological perturbation of cholesterol-lipid raft interactions by natural compounds like Rg3 enables broad-spectrum suppression of coexisting resistance mechanisms. It not only provides novel insights into the mechanisms underlying resistance in NSCLC but also presents a promising clinical strategy that could significantly improve treatment outcomes for patients.
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产品关联
DOI
PubMed
高影响因子
Materials Today Bio
·
2025
·
IF 10.2
Gen Li,Chunxiu Cai,Ning Zhang,Zijia Wang,Mingzhe Zhang,Quan Liu,Siyu Chen,Yanfei Shang,Chengqing Zhao,Shenzhen Ren,Hailong An
The calcium-activated chloride channel TMEM16A is frequently overexpressed in breast cancer, establishing a reciprocal activation loop with EGFR signaling pathways that play a crucial role in the proliferation of breast cancer. Consequently, the simultaneous targeting of TMEM16A and EGFR may be a promising, yet underexplored, therapeutic strategy for breast cancer. Herein, we developed a carrier-free polyphenol nanonetwork (PFGH) using procyanidin (PC), a natural polyphenolic TMEM16A inhibitor, via coordination with Fe 3+ , for co-delivering PC and gefitinib (Gef), an EGFR inhibitor. The resulting nanosystem, eliminating the requirement for additional nanocarriers, exhibited remarkable photothermal properties, pH-responsive drug release, and CD44-mediated tumor targeting. Functional assays confirmed that PFGH, under NIR irradiation, potently inhibited TMEM16A channel currents and exhibited superior antiproliferative effects compared to free PC, Gef, or their combination. RNA sequencing analysis confirmed the transcriptomic alterations in apoptosis, cell proliferation, and cancer-related pathways induced by the PFGH. In vivo studies further demonstrated that PFGH augments tumor-targeted combinatorial therapy, leveraging its photothermal properties, targeted co-delivery, and loop-suppressing activity. For the first time, our work presents a carrier-free polyphenol nanonetwork specifically engineered to co-target the TMEM16A-EGFR mutual activation loop, offering a novel, synergistic therapeutic approach for breast cancer.
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产品关联
DOI
PubMed
高影响因子
MICROCHEMICAL JOURNAL
·
2019
·
IF 3.206
Zhixiong Hu,Xin-Yue Jiao,Li Xu
The green tea leaf residue was used as the carbon source to produce carbon dots (named as T-CDs) by combining pyrolyzation at high temperature and oxidation by concentrated H 2 SO 4 . Owing to the co-doping of S and N, T-CDs possessed high fluorescence quantum yield up to 14.8%. The fluorescence of the T-CDs was stable to the environmental pH, ionic strength and ultraviolet radiation, but sensitive to temperature with switchable intensity between 15 °C and 65 °C. The fluorescence of T-CDs was also found to be quenched by gefitinib via the inner-filter effect. Thus, T-CDs were used as the fluorescence sensor for gefitinib determination with good linearity in the range of 0.1 μg/mL to 20 μg/mL with satisfactory accuracy. The proposed T-CDs were obtained based on waste recycling of tea leaf residue for sustainability, and this strategy widened the applications of CDs.
研究领域:
材料科学
·
环境科学
·
分析化学
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产品关联
DOI
高影响因子
危险品化学品经营许可证（带存储）