MOLECULES
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2022
·Vol. 27
·期 4
·1209
·
IF 4.927
Jiacheng He,Xianhua Lin,Fanhui Meng,Yumiao Zhao,Wei Wang,Yao Zhang,Xiaolei Chai,Ying Zhang,Weiwei Yu,Junjie Yang,Guichao Li,Xuekui Du,Hankun Zhang,Mingyao Liu,Weiqiang Lu
Metastatic pancreatic cancer remains a major clinical challenge, emphasizing the urgent need for the exploitation of novel therapeutic approaches with superior response. In this study, we demonstrate that the aberrant activation of prostaglandin E2(PGE2) receptor 4 (EP4) is a pro-metastatic signal in pancreatic cancer. To explore the therapeutic role of EP4 signaling, we developed a potent and selective EP4 antagonist L001 with single-nanomolar activity using a panel of cell functional assays. EP4 antagonism by L001 effectively repressed PGE2-elicited cell migration and the invasion of pancreatic cancer cells in a dose-dependent manner. Importantly, L001 alone or combined with the chemotherapy drug gemcitabine exhibited remarkably anti-metastasis activity in a pancreatic cancer hepatic metastasis model with excellent tolerability and safety. Mechanistically, EP4 blockade by L001 abrogated Yes-associated protein 1 (YAP)-driven pro-metastatic factor expression in pancreatic cancer cells. The suppression of YAP’s activity was also observed upon L001 treatment in vivo. Together, these findings support the notions that EP4–YAP signaling axis is a vital pro-metastatic pathway in pancreatic cancer and that EP4 inhibition with L001 may deliver a therapeutic benefit for patients with metastatic pancreatic cancer.Keywords:pancreatic cancer;metastasis;EP4;small molecule;YAP
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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DOI
PubMed
高影响因子
iScience
·
2024
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IF 4.6
Wei Yao,Yihui Wang,Xin Zhang,Yuhe Lin
Pancreatic cancer (PC) is one of the most lethal malignancies and new therapeutic strategies are urgently needed. β1,3-N-acetylglucosaminyltransferase V (B3GNT5) may be a potential option for cancer treatment, but its role in PC remains unknown. In this study, we first demonstrated through bioinformatics analysis that B3GNT5 was high expression in PC and predicted poor prognosis. We further constructed B3GNT5 overexpression or knockdown cell lines by employing lentivirus packaging techniques and confirmed that B3GNT5 could promote tumor cell viability and autonomous growth using cultured cells and vivo xenograft models. In addition, we found that knockdown of B3GNT5 in PC cells inhibited cell migration, invasion, and angiogenesis, as well as stemness of cancer stem cells and enhanced chemotherapy sensitivity to gemcitabine. Mechanistically, overexpression of the transcription factor STAT5B in PC cells enhanced the transcriptional activity of the B3GNT5 promoter. Our work confirmed a tumor-promotive role of B3GNT5 in PC pathogenesis.
研究领域:
肿瘤学
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分子生物学
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生物信息学
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产品关联
DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
·
2019
·Vol. 20
·期 12
·2988
·
IF 4.183
Xiuliang Zhu,Nan Lu,Ying Zhou,Shaoyan Xuan,Jiaojiao Zhang,Francesca Giampieri,Yongping Zhang,Fangfang Yang,Risheng Yu,Maurizio Battino,Zuhua Wang
Pancreatic cancer is a concealed and highly malignant tumor, and its early diagnosis plays an increasingly weighty role during the course of cancer treatment. In this study, we developed a polymeric magnetic resonance imaging (MRI) nanoplatform for MRI contrast agents. To improve tumor-targeting delivery of MRI contrast agents, we employed a pancreatic cancer targeting CKAAKN peptide to prepare a peptide-functionalized amphiphilic hyaluronic acid–vitamin E succinate polymer (CKAAKN–HA–VES) for delivering ultra-small superparamagnetic iron oxide (USPIO), namely, CKAAKN–HA–VES@USPIO. With the modification of the CKAAKN peptide, CKAAKN–HA–VES@USPIO could specifically internalize into CKAAKN-positive BxPC-3 cells. The CKAAKN–HA–VES@USPIO nanoparticles presented a more specific accumulation into pancreatic cancer cells than normal pancreatic cells, and an obvious decrease in signal intensity was observed in CKAAKN-positive BxPC-3 cells, compared with CKAAKN-negative HPDE6-C7 cells and non-targeting HA–VES@USPIO nanoparticles. The results demonstrated that our polymeric MRI nanoplatform could selectively internalize into CKAAKN-positive pancreatic cancer cells by the specific binding of CKAAKN peptide with pancreatic cancer cell membrane receptors, which provided a novel polymeric MRI contrast agent with high specificity for pancreatic cancer diagnosis, and makes it a very promising candidate for magnetic resonance imaging contrast enhancement.Keywords:pancreatic cancer;CKAAKN peptide;MRI contrast agent;polymer
研究领域:
肿瘤学
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医学影像学
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生物材料学
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DOI
PubMed
高影响因子
Cell Death Discovery
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2025
·Vol. 11
·期 1
·1-16
·
IF 7
Liang Xue,Tian Ruofei,Li Ting,Wang Hao,Qin Yifei,Qian Meirui,Fan Jing,Wang Dan,Cui Hong-Yong,Jiang Jianli
Pancreatic cancer exhibits high mortality rates with limited therapeutic options. Emerging evidence suggests that the ketogenic diet may act as adjuvant therapy by triggering ferroptosis in cancer cells, though the underlying molecular mechanisms remain unclear. This study aims to investigate the molecular mechanisms linking ketogenic metabolism and ferroptosis, with an emphasis on key regulatory proteins. We demonstrated that pancreatic adenocarcinoma (PAAD) tissues significantly enhanced ketogenic and ferroptosis phenotypes compared to normal tissues, both correlating with poorer patient prognosis. These phenotypes showed strong interdependence mediated by CAV1. In the pancreatic tumor microenvironment, CAV1 was predominantly expressed in tumor cells. Through in vitro cell experiments, we clarified that Na-OHB downregulated CAV1 expression in pancreatic cancer cells, inhibiting the transcription of the CAV1/AMPK/NRF2 downstream ferroptosis-protective genes SLC7A11 and SLC40A1. Additionally, we demonstrated the interaction between CAV1 and SLC7A11 molecules; when CAV1 was downregulated, it affected the stability of SLC7A11, leading to the ubiquitination and degradation of the translated SLC7A11 protein. Through these dual mechanisms, Na-OHB caused Fe 2+ overload, lipid peroxidation accumulation, and oxidative stress in pancreatic cancer cells, ultimately triggering ferroptosis. In ketogenic diet-fed tumor-bearing mouse models, we also observed a significant increase in lipid peroxidation and other related biomarkers, while CAV1 and SLC7A11 levels were markedly decreased compared to the normal diet group. Our findings identify CAV1 as a pivotal molecular link between ketogenic metabolism and ferroptosis in pancreatic cancer. The multi-level regulatory axis involving CAV1-mediated transcriptional regulation and post-translational modifications provides mechanistic insights into ketogenic diet-induced ferroptosis, suggesting potential therapeutic targets for pancreatic cancer adjuvant treatment.
研究领域:
肿瘤学
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分子生物学
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营养学
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产品关联
DOI
PubMed
高影响因子
Chemosensors
·
2022
·Vol. 10
·期 7
·276
·
IF 4.229
Kunhan Nie,Yongjian Jiang,Na Wang,Yajun Wang,Di Li,Lei Zhan,Chengzhi Huang,Chunmei Li
The abnormal expression of miRNA is closely related to the occurrence of pancreatic cancer. Herein, a programmable DNAzyme amplifier for the universal detection of pancreatic cancer-related miRNAs was proposed based on its programmability through the rational design of sequences. The fluorescence signal recovery of the DNAzyme amplifier showed a good linear relationship with the concentration of miR-10b in the range of 10–60 nM, with a detection limit of 893 pM. At the same time, this method displayed a high selectivity for miR-10b, with a remarkable discrimination of a single nucleotide difference. Furthermore, this method was also successfully used to detect miR-21 in the range of 10–60 nM based on the programmability of the DNA amplifier, exhibiting the universal application feasibility of this design. Overall, the proposed programmable DNAzyme cycle amplifier strategy shows promising potential for the simple, rapid, and universal detection of pancreatic cancer-related miRNAs, which is significant for improving the accuracy of pancreatic cancer diagnosis.Keywords:DNAzyme amplifier;signal amplification;miRNA detection;pancreatic cancer
研究领域:
分子生物学
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医学诊断
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生物化学
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产品关联
DOI
高影响因子
PeerJ
·
2024
·
IF 2.3
Zhaohong Wang,Hui Chen,Xufan Cai,Heqi Bu,Shengzhang Lin
Background Andrographolide (Andro), an extract of Andrographis paniculate (Burm.f.) Wall. ex Nees (Acanthaceae), possesses diverse biologically active properties. However, the precise mechanisms and effects of Andro on pancreatic cancer (PC) remain unclear. Methods The cytotoxic potential of Andro and underlying mechanism towards PC cells was investigated through in vitro experiments and a xenograft mouse model. PC cells were first subjected to varying concentrations of Andro. The reactive oxygen species (ROS) was assessed using flow cytometry and DCFH-DA staining. The apoptosis rate was detected by flow cytometry. Additionally, western blot was applied to evaluate the expression levels of cleaved-caspase-3, DJ-1, LC3-I, LC3-II, and p62. To further elucidate the involvement of ROS accumulation and autophagy, we employed N-acetylcysteine as a scavenger of ROS and 3-Methyladenine as an inhibitor of autophagy. Results Andro demonstrated potent anti-proliferative effects on PC cells and induced apoptosis, both in vitro and in vivo . The cytotoxicity of Andro on PC cells was counteracted by DJ-1 overexpression. The reduction in DJ-1 expression caused by Andro led to ROS accumulation, subsequently inhibiting the growth of PC cells. Furthermore, Andro stimulated cytoprotective autophagy, thus weakening the antitumor effect. Pharmacological blockade of autophagy further enhanced the antitumor efficacy of Andro. Conclusion Our study indicated that ROS accumulation induced by the DJ-1 reduction played a key role in Andro-mediated PC cell inhibition. Furthermore, the protective autophagy induced by the Andro in PC cells is a mechanism that needs to be addressed in future studies.
研究领域:
肿瘤学
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药理学
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细胞生物学
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产品关联
DOI
PubMed
高影响因子
Small
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2025
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IF 12.1
Li-Li Xu,Ming Wang,Yi-Ke Wang,Yi-Jing Chen,Yu-Xin Zhang,Yan-Qiu Zhang,Shi-Bo Cheng,Min Xie,Wei-Hua Huang
Microchip-based exosome analysis has emerged as a promising approach for liquid biopsy in cancer diagnosis, treatment monitoring, and prognostic evaluation. However, current microchips for exosome analysis typically rely on planar, 2D channel structures with affinity properties, which require complex fabrication but deliver suboptimal separation and detection performance. This study presents a novel vessel-like microtunnel chip, integrated with biomimetic octopus tentacles, achieving an exosome isolation efficiency of 90.4%. The innovative design incorporates interwoven, 3D micropathways, enhancing fluid dynamics and promoting efficient mixing between exosomes and microchannels. Nanofiber-coated silicon microspheres, functionalized with synthetic peptides, mimic octopus tentacles to anchor the microtunnels, dynamically extending under fluid shear forces to specifically recognize lipid bilayer structures for exosome capture. This platform incorporates enzyme-catalyzed signal amplification using Au nanoprobes for colorimetric detection to sensitively analyze four protein markers on plasma-derived exosomes from 60 clinical samples. Machine learning is used to develop a diagnostic model, achieving an area under the curve (AUC) of 0.9888 in distinguishing pancreatic cancer from pancreatitis and healthy controls. This approach provides a rapid, sensitive, accurate, and user-friendly method for pancreatic cancer diagnosis, addressing the clinical challenges of early detection and the frequent misdiagnosis of pancreatic cancer as pancreatitis.
研究领域:
医学
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生物工程
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肿瘤学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Nanomedicine
·
2024
·
IF 4.7
Shuhui Li,Yuansheng Liu,Xiaojun Sui,Yuzhen Zhuo,He Siqi,Zhang Sijia,Zhang Hui,Li Dihua,Zhang Dapeng,Yang Lei
Aim: To evaluate the anti-pancreatic cancer effect of novel Tubeimoside I multifunctional liposomes combined with gemcitabine.Methods: Liposomes were prepared through the thin film hydration method, with evaluations conducted on parameters including encapsulation efficiency (EE%), particle size, polydispersity index (PDI), zeta potential (ZP), storage stability, and release over a 7-day period. The cellular uptake rate, therapeutic efficacy in vitro and in vivo and the role of immune microenvironment modulation were evaluated.Results: The novel Tubeimoside I multifunctional liposomal exhibited good stability, significant anti-cancer activity, and immune microenvironment remodeling effects. Furthermore, it showed a safety profile.Conclusion: This study underscores the potential of Novel Tubeimoside I multifunctional liposomal as a promising treatment option for pancreatic cancer.
研究领域:
药理学
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肿瘤学
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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
Drug Design Development and Therapy
·
2022
·
IF 4.319
Na Yin,Hui Yu,Xiaodi Zhang,Xiaodan Lv
Purpose Pancreatic cancer (PCa) is projected to become the second leading cause of cancer-related deaths by 2030. Gemcitabine (GEM) combined with erlotinib (ERL) have been approved by the FDA for locally advanced, unresectable or metastatic pancreatic cancer therapy since 2005. Type-1 matrix metalloproteinase (MT1-MMP) has been recognized as a critical mediator of several steps in PCa progression including activating TGF-β or releasing latent TGF-β from LTBP-1, resulting in increased collagen production and cleavage collagen.Methods In the present research, GEM and ERL co-loaded nanoparticles (GEM/ERL NPs) were prepared. A non-substrate MT1-MMP binding peptide was decorated onto the GEM/ERL NPs surface.Results M-M GEM/ERL NPs exhibited the highest uptake ability (67.65 ± 2.87%), longest half-life period, largest area under the curve, and the best tumor inhibition efficiency (69.81 ± 4.13%). The body weight, blood urine nitrogen (BUN), aspartate aminotransferase (AST), and alanine aminotransferase (ALT) of the system were steady when tested in mice model.Conclusion In conclusion, M-M GEM/ERL NPs protected the drugs in the plasma, improved cellular uptake capacity, exhibited the most remarkable tumor cell inhibition ability, and showed the most efficient tumor growth inhibition capacity in vivo. M-M GEM/ERL NPs could be applied as an efficient and safe system for the synergistic combination chemotherapy of PCa.
研究领域:
肿瘤学
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药剂学
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分子生物学
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产品关联
DOI
PubMed
高影响因子
Scientific Reports
·
2025
·Vol. 15
·期 1
·1-12
·
IF 3.9
Li Silong,Li Na,Yin Qiangqiang,Zhang Zhichen,Hu Haifeng,Hao Liguo
This project aims to construct cRGD functionalized mesoporous silica nanoparticles and cRGD modified mesoporous silica nanoparticles for the diagnosis and treatment of tumors, providing new ideas for targeted therapy of tumors. The mesoporous silica nanoparticles were doped with gadolinium in situ to provide excellent imaging; cRGD was coupled on the particle surface to confer particle targeting; and hyaluronic acid was loaded onto the particles by electrostatic adsorption, thereby improving the biocompatibility of the particles and prolonging their in vivo circulation time.Taking pancreatic cancer as a model, we studied its targeting ability to pancreatic cancer and its phagocytosis to cancer cells; Using methods such as cell growth experiments and flow cytometry, the anti-cancer effect and pro apoptotic effect of the system were studied. In vivo distribution, tumor targeting and therapeutic efficacy of nanoparticles evaluated in a mouse model of pancreatic cancer with loaded tumors.Evaluate the bioavailability and enrichment of nanoparticles in tumor tissue using MRI technology. Evaluate the therapeutic effect and safety through changes in tumor volume, histopathological examination, and prognosis. Characterization of the synthesis results proved that cRGD-HA-DOX-Gd 2 O 3 @MSN (cHDG@MSN) was successfully synthesized with a particle size of 230.83 ± 12.36 nm.In vitro drug release experiments of DOX were carried out at different pH values (5.5 and 7.4), where the release was only up to 22.65% at pH 7.4, whereas DOX release was increased up to 78.75% at pH = 5.5.The results confirm the pH responsiveness of this nanocarrier platform.The results of cytotoxicity studies showed that cHDG@MSN itself is not cytotoxic. Biosafety evaluation and hemolysis test results confirmed that the probe is highly biocompatible.Notably, Gd 3+ significantly enhanced the T 1 contrast of the system according to MR imaging results.The apoptosis rates of SW1990 cells treated with PBS, DOX and cHDG@MSN in flow cytometry were 13.97%, 18.38% and 29.02%, respectively, demonstrating the effectiveness of the nanoprobes at the cellular level. Animal experiments demonstrated the effectiveness of nanoprobes at the pathological level and imaging level.Cells and animals demonstrated that cHDG@MSN effectively inhibited the proliferation of pancreatic cancer cells. This research further verified the pH sensitivity of the constructed compound drug delivery system to achieve accurate diagnosis and treatment of pancreatic cancer tumor cells.
研究领域:
肿瘤学
·
纳米医学
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影像医学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Carbohydrate Polymer Technologies and Applications
·
2025
·
IF 6.5
Yi Wang,Yabin Ding,Xiaomei Wei,Wenxiu Tian,Wenxiang Zheng,Yongliang Liu,Chuanqin Shi,Xinxin Xiang
Pancreatic ductal adenocarcinoma (PDAC) presents a significant clinical challenge due to its high mortality and resistance to chemotherapy. Over the past decade, fucoidan has been explored as a potential treatment for cancers of the lung, breast, bladder, colon, and pancreas. However, investigations into the efficacy of fucoidan within the tumor microenvironment (TME) of pancreatic cancer are scarce, and its governing mechanisms are not fully understood. Herein, fucoidan (Mfu) from Fucus vesiculosus significantly induced the mRNA expression of inflammatory cytokines (interleukin (IL)-1β, IL-6, and tumor necrosis factor (TNF)-ɑ) by real-time fluorescence quantitative PCR (qPCR) in macrophages. RNA spatial transcriptome sequencing and western blotting showed that Mfu specifically targeted the tumor necrosis factor receptor superfamily member 9 (4-1BB), thereby triggering the TNF signaling pathway in RAW 264.7 cells. Mfu-activated macrophages indirectly elicited the apoptosis and G1-phase arrest of PAN02 cells, as shown by apoptotic protein detection and flow cytometry, suggesting a regulatory effect on pancreatic cancer cell death. In a PDAC allograft model in mice, Mfu (100–400 mg/kg/day, oral gavage) exhibited robust anti-tumor efficacy. Besides, immunohistochemistry (IHC) revealed that Mfu targeted 4-1BB specifically to activate macrophages within the TME. By engaging with the 4-1BB receptor and activating macrophages, Mfu offers a promising strategy to advance the development of pancreatic cancer immunotherapy.
研究领域:
肿瘤学
·
免疫学
·
分子生物学
✓ 已验证
产品关联
DOI
高影响因子
JOURNAL OF CONTROLLED RELEASE
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2024
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IF 10.5
Shuang Zhu,Chenglu Gu,Long Gao,Shuanglong Du,Duiping Feng,Zhanjun Gu
Pancreatic ductal adenocarcinoma (PDAC) has a low survival rate and limited treatment options. Concurrent chemoradiotherapy is considered beneficial to improve tumor control, but the low drug bioavailability at tumor site and the low radiation tolerance of surrounding healthy organs greatly limits its effectiveness. Lipiodol, a natural drug carrier used in clinical transarterial chemoembolization, has shown potential as a radiosensitizer due to its high Z element iodine composition. Thus, this study aims to repurpose lipiodol as a sensitizer to simultaneously enhance chemo- and radiotherapy for PDAC. To this end, a stable lipiodol emulsion (IOE) loaded with gemcitabine is designed using clinically approved surfactants. At in vivo level, IOE demonstrates better radiotherapeutic effect than existing nanoradiosensitizers and enhanced drug bioavailability over free drug, leading to significant tumor inhibition and improved survival rates under concurrent chemo-radiotherapy. This may due to the sustained drug release, homogenous spatial distribution, and long-term retention ability of IOE in solid PDAC tumor. Furthermore, to better understand the functioning mechanism of drug-loaded IOE, in vitro study is conducted to reveal the ROS- and DNA damage-related therapeutic pathways. Lastly, a comprehensive toxicity assessment also proves the good biocompatibility and safety of as-prepared IOE. This study offers a clinically feasible sensitizer for simultaneous chemoradiotherapy and holds potential for other types of cancer treatment in clinics.
研究领域:
肿瘤学
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放射治疗学
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药剂学
✓ 已验证
DOI
高影响因子
危险品化学品经营许可证（带存储）