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
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免疫学
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药理学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Journal of Biomaterials and Tissue Engineering
·
2018
·Vol. 8
·期 3
·426-432
·
IF 0.781
Hu Jinghui,Wang Li,Shen Heping,Huang Yujie,Zhao Wei
The elevated expression of mammalian target of rapamycin (mTOR) is associated with the occurrence, progression, and drug resistance of various tumors. Studies have shown overexpression of mTOR and reduced expression of miR-101 in cervical cancer tissues. Bioinformatic analysis has revealed
that a targeting binding site exists between miR-101 and the 3'-UTR of mTOR mRNA. In this study we determined whether miR-101 played a role in regulating mTOR expression and influencing the proliferation, apoptosis, and drug resistance to cisplatin (DDP) of CC cells. The regulatory relationship
between miR-101 and mTOR was validated by dual-luciferase reporter gene assay. The DDP resistance cell line, CaSki/DDP, was established, and the expressions of miR-101, mTOR, p-mTOR, and p-4EBP1 in the CaSki/DDP cell line and parental CaSki cells. The effect of DDP treatment on the proliferation
and apoptosis of the two cell lines were detected by flow cytometry. CaSki/DDP cells were divided into the following four transfection groups: miR-NC group; miR-101 mimic group; si-NC group; and si-mTOR group. The expression of miR-101, MTOR, p-mTOR, and p-4EBP1 was determined, and the effect
of DDP treatment on the proliferation and apoptosis of the two cell lines we detected by flow cytometry. There was a targeted regulatory relationship between miR-101 and mTOR. The expression and apoptosis rate of miR-101 in CaSki/DDP cells were significantly lower than CaSki cells, while the
expression and proliferation of mTOR, p-mTOR, and p-4EBP1 in CaSki/DDP cells were significantly higher than CaSki cells. The transfection of miR-101 mimic or si-mTOR significantly reduced the expression of mTOR, p-mTOR, and p-4EBP1 in CaSki/DDP cells and weakened the cell proliferation ability.
DDP treatment significantly increased the apoptosis rate. The decreased expression of miR-101 is associated with CaSki/DD cell resistance to DDP. Overexpression of miR-101 can reduce the resistance of cervical cancer CaSki/DDP cells to DDP by targeted inhibition of the expression of mTOR.
研究领域:
肿瘤学
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分子生物学
·
癌症研究
✓ 已验证
DOI
高影响因子
BIOMEDICINE & PHARMACOTHERAPY
·
2024
·
IF 6.9
Weikang Guo,Wanyue Wang,Fei Lei,Ruxin Zheng,Xinyao Zhao,Yuze Gu,Mengdi Yang,Yunshun Tong,Yaoxian Wang
Cisplatin (DDP) resistance poses a significant challenge in the treatment of ovarian cancer. Studies have shown that the combination of certain polysaccharides derived from plants with DDP is an effective approach to overcoming drug resistance in some cancers. Angelica sinensis (Oliv.) Diels has been used for centuries in China to treat gynecological ailments. Numerous studies indicate that Angelica sinensis polysaccharide (ASP), an extract from Angelica sinensis , can inhibit various forms of cancer. However, the impact of ASP on ovarian cancer remains unexplored. Through both in vitro and in vivo experiments, our study revealed the capability of ASP to effectively reversing DDP resistance in cisplatin-resistant ovarian cancer cells, while exhibiting acceptable safety profiles in vivo. To elucidate the mechanism underlying drug resistance reversal, we employed RNA-seq analysis and identified GPX4 as a key gene. Considering the role of GPX4 in ferroptosis, we conducted additional research to explore the effects of combining ASP with DDP on SKOV3/DDP cells. In summary, our findings demonstrate that the combination of ASP and DDP effectively suppresses GPX4 expression in SKOV3/DDP cells, thereby reversing their resistance to DDP.
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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植物科学
✓ 已验证
DOI
PubMed
高影响因子
CURRENT CANCER DRUG TARGETS
·
2023
·Vol. 24
·期 4
·445-454
·
IF 3
Wu Min,Jin Meng-Meng,Cao Xiao-Hui,Zhao Lei,Li Yong-Huai
Background: Previous studies have proposed that the transcriptional regulatory factor tripartite motif containing 29 (TRIM29) is involved in carcinogenesis via binding with nucleic acid. TRIM29 is confirmed to be highly expressed when the cancer cells acquire therapy-resistant properties.
We noticed that TRIM29 levels were significantly increased in anlotinib-resistant NCIH1975 (NCI-H1975/AR) cells via mining data information from gene expression omnibus (GEO) gene microarray (GSE142031; log2 fold change > 1, p < 0.05). Objective: Our study aimed to investigate the
function of TRIM29 on the resistance to anlotinib in non-small cell lung cancer (NSCLC) cells, including NCI-H1975 and A549 cells. Methods: Real-time RT-PCR and western blot were used to detect TRIM29 expression in anlotinib- resistant NSCLC (NSCLC/AR) cells. Apoptosis were determined
through flow cytometry, acridine orange/ethidium bromide staining as well as western blot. ELISA was used to measure the content of C-X3-C motif chemokine ligand 1. Co-Immunoprecipitation assay was performed to verify the interaction between TRIM29 and RAD50 double-strand break repair protein
(RAD50). Results: TRIM29 expression was shown to be elevated in the cytoplasm and nucleus of NSCLC/ AR cells compared to normal NSCLC cells. Next, we demonstrated that TRIM29 knockdown facilitated apoptosis and enhanced the sensitivity to anlotinib in NSCLC/AR cells. Based on the refined
results citing from the database BioGRID, it was proved that TRIM29 interacted with RAD50. Herein, RAD50 overexpression diminished the pro-apoptotic effect induced by silencing TRIM29 in anlotinib-resistant A549 (A549/AR) cells. Conclusion: Finally, we concluded that the increased sensitivity
to anlotinib in NSCLC/AR cells was achieved by knocking down TRIM29, besides, the positive effects of TRIM29 knockdown were attributed to the promotion of apoptosis via binding to RAD50 in NSCLC/AR cell nucleus. Therefore, TRIM29 might become a potential target for overcoming anlotinib
resistance in NSCLC treatment.
研究领域:
肿瘤学
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分子生物学
·
药理学
✓ 已验证
DOI
PubMed
高影响因子
Frontiers in Oncology
·
2025
·
IF 3.3
Keke Shang,Yang Chen,Jingjie Jin,Tong Wang,Gong Zhang
Genome instability, a hallmark of cancer, leads to endless mutations that eventually cause drug resistance against almost all chemotherapy drugs. This poses a significant obstacle to the success of cancer treatments. Here, we report that aurintricarboxylic acid (ATCA) effectively suppresses the malignant phenotypes, including proliferation, migration, invasion, and clone formation, of cancer cells of multiple cancers, including cisplatin-resistant lung cancer cells, paclitaxel-resistant lung cancer cells, and doxorubicin-resistant breast cancer cells. Interestingly, ATCA does not cause acute cytotoxicity. Proteome analysis of the whole proteome and nascent chains showed that ATCA reduced translation initiation and thus reduced the abundance of the highly abundant respiratory chain complex. This lowered the potential of the mitochondrial membrane and thus restricted the energy production. This principle could be hardly circumvented by cancer cells and thus may serve as a promising and universal candidate for a second-line therapeutic agent to control cancer progression after drug resistance.
研究领域:
肿瘤学
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分子生物学
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药理学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF NANOBIOTECHNOLOGY
·
2025
·Vol. 23
·期 1
·1-22
·
IF 12.6
Zhang Lian-Ying,Chen Xiao-Tong,Li Rong-Tian,Meng Wei,Huang Guo-Qin,Chen Yong-Jian,Ge Feng-Jun,Zhang Qun,Quan Yu-Jun,Zhang Cai-Tao,Liu Yi-Fei,Chen Ming,Chen Jin-Xiang
Breast cancer (BC) is a significant cause of cancer-related deaths among women worldwide. Hypoxia, a common feature of solid tumor, is associated with drug resistance and a poor prognosis in BC. In this study, we present a strategy to overcome hypoxia-induced chemotherapy tolerance in BC. Specifically, we synthesized a hollow gold (Au)-platinum (Pt) bimetallic nanoshell for the first time, which acted as a drug delivery system (DDS) for doxorubicin (DOX). The photothermal effect, induced by the surface plasmon resonance (SPR) from the Au-Pt shell under near infrared-II (NIR-II) laser irradiation, not only directly causes tumor cell death through photothermal therapy (PTT), but also significantly enhances the catalase-like activity between Pt nanoparticles and endogenous H 2 O 2 . This, subsequently, results in a heightened yield of O 2 , which further facilitates the release of DOX. This process alleviates tumor hypoxia and down-regulating hypoxia-inducible factor-1α (HIF-1α), multidrug resistance gene 1 (MDR1), and P-glycoprotein (P-gp), which can reverse drug resistance and achieve more effective DOX chemotherapy effects. Significantly, the increased availability of oxygen further re-polarizes immunosuppressive M2 macrophages into antitumor M1 macrophages. This study presents a novel strategy to tackle tumor proliferation and enhance tumor response to chemotherapy, offering hope for reversing in drug resistance in cancerous lesions. Graphical
研究领域:
肿瘤学
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药理学
·
纳米医学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
NATURE MATERIALS
·
2025
·
IF 38.5
Liu Huayang,Song Zilin,Zhang Yu,Wu Bihan,Chen Dinghao,Zhou Ziao,Zhang Hongyue,Li Sangshuang,Feng Xinping,Huang Jing,Wang Huaimin
Bioinspired materials based on self-assembling peptides are promising for tackling various challenges in biomedical engineering. While contemporary data-driven approaches have led to the discovery of self-assembling peptides with various structures and properties, predicting the functionalities of these materials is still challenging. Here we describe the deep learning-guided de novo design of antimicrobial materials based on self-assembling peptides targeting bacterial membranes to address the emerging problem of bacterial drug resistance. Our approach integrates non-natural amino acids for enhanced peptide self-assembly and effectively predicts the functional activity of the self-assembling peptide materials with minimal experimental annotation. The designed self-assembling peptide leader displays excellent in vivo therapeutic efficacy against intestinal bacterial infection in mice. Moreover, it exhibits an enhanced biofilm eradication capability and does not induce acquired drug resistance. Mechanistic studies reveal that the designed peptide can self-assemble on bacterial membranes to form nanofibrous structures for killing multidrug-resistant bacteria. This work thus provides a strategy to discover functional peptide materials by customized design.
研究领域:
生物医学工程
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材料科学
·
人工智能
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Advanced Healthcare Materials
·
2018
·Vol. 7
·期 13
·1701370
·
IF 5.609
Haiwei Ji,Li Wu,Fang Pu,Jinsong Ren,Xiaogang Qu
The rapid, simple, and reliable identification of the most prevalent pathogens is essential for clinical diagnostics, biology, and food safety. Herein, four protein-encapsulated gold nanoclusters (protein–AuNCs) are designed and prepared as a sensor array for rapid identification of bacteria. The discrimination of six kinds of bacteria, including two kinds of drug-resistant bacteria, is successfully realized by the as-fabricated sensor array. The strategy presented here shows the advantages of easy synthesis and convenient to use. Furthermore, 100% classification accuracy is achieved by the sensor array consisting of two protein–AuNCs probes, demonstrating the design with sufficient diagnostic capacity. Taken together, the developed sensor array holds great promise for facile diagnosis of bacterial infection in resource-limited settings.
研究领域:
临床诊断
·
生物技术
·
食品安全
✓ 已验证
DOI
PubMed
高影响因子
Frontiers in Pharmacology
·
2024
·
IF 4.4
Lu Yixing,Qiao Weimei,Xue Yaqian,Hong Xiaoxin,Jin Yuhang,Li Jie,Peng Xianfeng,Zeng Dongping,Zeng Zhenling
Introduction: Riemerella anatipestifer (R. anatipestifer) is an important pathogen in waterfowl, leading to substantial economic losses. In recent years, there has been a notable escalation in the drug resistance rate of R. anatipestifer. Consequently, there is an imperative need to expedite the development of novel antibacterial medications to effectively manage the infection caused by R. anatipestifer.Methods: This study investigated the in vitro and in vivo antibacterial activities of a novel substituted benzene guanidine analog, namely, isopropoxy benzene guanidine (IBG), against R. anatipestifer by using the microdilution method, time-killing curve, and a pericarditis model. The possible mechanisms of these activities were explored.Results and Discussion: The minimal inhibitory concentration (MIC) range of IBG for R. anatipestifer was 0.5–2 μg/mL. Time-killing curves showed a concentration-dependent antibacterial effect. IBG alone or in combination with gentamicin significantly reduced the bacterial load of R. anatipestifer in the pericarditis model. Serial-passage mutagenicity assays showed a low probability for developing IBG resistance. Mechanistic studies suggested that IBG induced membrane damage by binding to phosphatidylglycerol and cardiolipin, leading to an imbalance in membrane potential and the transmembrane proton gradient, as well as the decreased of intracellular adenosine triphosphate. In summary, IBG is a potential antibacterial for controlling R. anatipestifer infections.
研究领域:
微生物学
·
兽医学
·
药理学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
CANCER BIOLOGY & THERAPY
·
2020
·
IF 3.659
Chunhua Zhou,Wencheng Kong,Tongfa Ju,Qi Xie,Lulu Zhai
Background Studies showed that microRNAs (miRNAs) are important regulators in drug resistance. The current study investigated the role of miR-185-3p and its predicted target gene AQP5 in 5-FU-insensitive colorectal cancer (CRC) cells.Methods Quantitative real-time polymerase chain reaction (qRT-PCR) and Spearman’s correlation analysis were conducted to determine the correlation of expression levels of miR-185-3p and AQP5 from CRC tissues. HCT-116 and HCT-8 cells were treated by gradient concentration of 5-FU to construct 5-FU-resistant CRC model. The inhibition and viability of 5-FU-resistant cells were detected by MTT assay, and cell migration and invasion ability were determined by wound healing and transwell assay. The expressions of miR-185-3p and AQP5 were measured by qRT-PCR. StarBase and dual-luciferase reporter assay were used to predict and confirm the interaction between miR-185-3p and AQP5. Further experiments were performed to explore the function of miR-185-3p in 5-FU-resistant cells through regulating aquaporin-5 (AQP5). The levels of EMT-associated markers and AQP5 were determined by conducting Western Blot and qRT-PCR.Results We found that 5-FU-resistant CRC cells showed a lower inhibition rate, and higher migration and invasion abilities. MiR-185-3p was low-expressed in CRC tissues and 5-FU-resistance cells, and it targeted and regulated the expression of AQP5, which was found up-regulated in CRC and 5-FU-resistance CRC cells (r = −0.29, P < .05). Furthermore, miR-185-3p mimic enhanced the chemo-sensitivity of 5-FU-resistant cells, while overexpressed AQP5 reversed such an effect produced by miR-185-3p mimic.Conclusion MiR-185-3p mimic enhances the chemosensitivity of CRC cells via AQP5. Our research provides a potential therapeutic target for 5-FU-resistant CRC cells.
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
PHARMAZIE
·
2018
·Vol. 73
·期 12
·729-732
·
IF 1.016
Wang YB.,Sun B.,Han B.
Malignant melanoma is a highly lethal disease, and advanced stages of melanoma have proven to be resistant to many chemotherapeutic drugs including temozolomide and paclitaxel. Cancer stem cells (CSCs) have been identified and isolated in different cancers including melanoma, and have
been proven playing important role in the drug resistance. Retinoic acid (RA) is a promising anticancer agent, which can induce differentiation of CSCs. The main purpose of the present study was to evaluate the possible RA-induced differentiation of melanoma CSCs and sensitization of melanoma
CSCs to paclitaxel. Our results show that CSCs of human melanoma A375 cells was more tolerant to paclitaxel than other non-CSCs melanoma cells. On the contrary, RA had stronger inhibitory effect on melanoma CSCs than on non-CSCs. At the same time, RA could arrest the cell cycle of CSCs and
reduce the expression of Sox-2, Oct-4 in CSCs of melanoma, thereby induced the differentiation of CSCs and increased its sensitivity to paclitaxel. With this study we concluded that RA increases the anticancer effect of paclitaxel by inducing differentiation of cancer stem cells in melanoma,
and the combined application of RA and paclitaxel may be more effective in the treatment of melanoma.
研究领域:
肿瘤学
·
细胞生物学
·
药理学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF SOL-GEL SCIENCE AND TECHNOLOGY
·
2024
·
IF 2.3
Yang Guoqiang,Hong Ye,Wang Yimei,Shi Xuechao,Hou Shuxian,Liu Xinxin,Wang Yuxuan,Ge Fei,Wang Jun
It is well known that bacterial infections pose a great threat to human health and life, and the situation has intensified because of the emergence of drug-resistant bacteria, especially in the medical field, the number of deaths due to super-bacteria infections that result from antibiotic misuse continues to increase every year. Researchers have been working hard and trying to find a suitable method to fight against bacterial infections, however, there is still no effective method to fight drug-resistant bacterial infections. In this study, an ultra-facile strategy was built to synthesize Copper Oxide Nanoclusters (CuO NCs), that exhibited broad-spectrum bactericidal activity against common pathogenic Gram-positive and Gram-negative bacteria. The synthesized CuO NCs exhibited a cluster structure with good stability and biocompatibility. The antibacterial mechanism revealed that the synthesized CuO NCs can cause bacterial death in multiple ways, including disrupting the bacterial cell membrane and ablating the biofilm, inducing the generation of ROS, and leading to nucleic acid leakage of bacteria. CuO NCs are simple to synthesize, have strong antibacterial activity, and are expected to open new avenues of antibacterial activity in the severe antibiotic environment due to the combination of antibacterial mechanisms that make it difficult for bacteria to develop drug resistance quickly. Graphical In this study, we designed and synthesized copper oxide nanoclusters (CuO NCs) with favorable biosafety and stability for combating bacterial infection problems. The material possesses several advantages that including: (1) CuO NCs are synthesized in a straightforward and expeditious method. (2) CuO NCs have been demonstrated to possess good biocompatibility. (3) The synthesized CuO NCs exhibit broad-spectrum antimicrobial activity against E. coli and S. aureus , as well as for their drug-resistant strains. (4) The synthesized CuO NCs are capable of effectively removing biofilms formed by bacteria and promoting ROS generation, which disrupts the bacterial cell membrane, induces nucleic acid leakage, and ultimately cause the death of bacteria. This study employing an efficient strategy to synthesize CuO NCs with excellent broad-spectrum anti-bacterial ability, offering a promising method for addressing the growing challenge of multi-drug resistant bacteria.
研究领域:
生物医学
·
材料科学
·
微生物学
✓ 已验证
产品关联
DOI
高影响因子
危险品化学品经营许可证（带存储）