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Flavonoids of Rosa rugosa Thunb.inhibit tumor proliferation and metastasis in human hepatocellular carcinoma HepG2 cells

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Food Science and Human Wellness 2022年第2期11卷 374-382页

作者： Zhiguo Zhang Meilin Wang Shu Xing Chen Zhang School of Food Science and Engineering Qilu University of Technology(Shandong Academy of Sciences)Jinan 250353China School of Chemistry and Pharmaceutical Engineering Qilu University of Technology(Shandong Academy of Sciences)Jinan 250353China School of Science The Hong Kong University of Science and TechnologyHong KongChina

Rosa rugosa Thunb.is recognized as both medicine and edible in China.The article investigated the antitumor activity of rose flavonoids.Water-extracted rose flavonoids(RFW)and ethanol-extracted rose flavonoids(RFE)were achieved by extracting with distilled water and 70%ethanol,respectively.The effects of the two extracts on proliferation inhibition,apoptosis inducement and metastasis prevention of human HepG2 hepatocellular carcinoma cell lines were tested,via optical/fluorescence microscopy,MTT detection,Transwell assay,flow cytometry and Western blot,etc.The results indicated that rose flavonoids at low concentration(10-40μg/mL)had a better inhibitory effect on migration and invasion of HepG2 cells in a dose-dependent manner,while rose flavonoids at high concentration(80-160μg/mL)could induce apoptosis of HepG2 cells by up-regulating the expression of pro-apoptotic proteins p53 and Bax,and down-regulating the expression of anti-apoptotic proteins Bcl-2,leading to the functioning of caspase-3 and caspase-9.The effect of RFE at the same concentration was significantly better than that of RFW.Conclusion,this study found that rose flavonoids had a certain inhibitory effect on proliferation and metastasis of human liver cancer cells HepG2,indicating the application of rose flavonoids in preventing and treating of liver cancer.

关键词： Rose flavonoids tumor metastasis Apoptosis Human liver cancer

FAM53B promotes pancreatic ductal adenocarcinoma metastasis by regulating macrophage M2 polarization

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World Journal of Gastrointestinal Oncology 2024年第4期16卷 1479-1499页

作者： Xuan-Zeng Pei Min Cai Da-Wei Jiang Song-Hai Chen Qing-Qing Wang Hui-Min Lu Yi-Fan Lu Department of Hepatological Surgery The First Hospital of JiaxingJiaxing 314000Zhejiang ProvinceChina Department of General Surgery West China Hospital of Sichuan UniversityChengdu 610044Sichuan ProvinceChina

BACKGROUND Our study investigated the role of FAM53B in regulating macrophage M2 polarization and its potential mechanisms in promoting pancreatic ductal adenocarcinoma(PDAC)metastasis.AIM To further investigate the role of FAM53B in regulating macrophage M2 polarization and its potential mechanism in promoting PDAC metastasis.Our goal is to determine how FAM53B affects macrophage M2 polarization and to define its underlying mechanism in PDAC metastasis.METHODS Cell culture and various experiments,including protein analysis,immunohisto-chemistry,and animal model experiments,were conducted.We compared FAM53B expression between PDAC tissues and healthy tissues and assessed the correlation of FAM53B expression with clinical features.Our study analyzed the role of FAM53B in macrophage M2 polarization in vitro by examining the expression of relevant markers.Finally,we used a murine model to study the role of FAM53B in PDAC metastasis and analyzed the potential underlying mechanisms.RESULTS Our research showed that there was a significant increase in FAM53B levels in PDAC tissues,which was linked to adverse tumor features.Experimental findings indicated that FAM53B can enhance macrophage M2 polarization,leading to increased anti-inflammatory factor release.The results from the mouse model further supported the role of FAM53B in PDAC metastasis,as blocking FAM53B prevented tumor cell invasion and metastasis.CONCLUSION FAM53B promotes PDAC metastasis by regulating macrophage M2 polarization.This discovery could lead to the development of new strategies for treating PDAC.For example,interfering with the FAM53B signaling pathway may prevent cancer spread.Our research findings also provide important information for expanding our understanding of PDAC pathogenesis.

关键词： FAM53B Pancreatic ductal adenocarcinoma tumor metastasis Macrophage polarization

tumor‑Anchoring Drug‑Loaded Fibrous Microspheres for MR Imaging‑Guided Local Chemotherapy and metastasis Inhibition

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Advanced Fiber Materials 2022年第4期4卷 807-819页

作者： Beilei Zhang Yue Gao Rui Yang Zhijun Ouyang Hongwei Yu Han Wang Xiangyang Shi Mingwu Shen State Key Laboratory for Modification of Chemical Fibers and Polymer Materials Shanghai Engineering Research Center of Nano‑Biomaterials and Regenerative MedicineCollege of ChemistryChemical Engineering and BiotechnologyDonghua UniversityShanghai 201620China CQM-Centro de Quimica da Madeira Universidade da Madeira9020‑105 FunchalPortugal Department of Radiology Shanghai General HospitalShanghai Jiao Tong University School of MedicineShanghai 200080China

Unobtrusive metastasis and invasion of malignant tumors are major causes for the death of cancer patients,and unfortunately the lack of specificity and abrupt release of anticancer drugs applied to the primary tumors are causing serious side effects in cancer management.Hence,the development of controlled local drug delivery systems that can effectively treat primary tumors and inhibit tumor metastasis is of critical importance for improved cancer therapeutics.Herein,we developed hyaluronic acid(HA)-modified porous fibrous microspheres as a drug delivery system with the functions of long-acting local chemotherapy,tumor metastasis inhibition and magnetic resonance(MR)imaging.Poly(lactic-co-glycolic acid)(PLGA)short fibers obtained by combined electrospinning and homogenization techniques were successfully modified with gadolinium(Gd^(3+))chelates and HA,which were subsequently mixed with doxorubicin(DOX)to obtain the multifunctional drug-loaded fibrous microspheres of DOX-PLGA-PEI-DTPA-Gd/HA(DOX−PGH)by electrospray and further crosslinking.The developed DOX−PGH microspheres with an average diameter of 118.8μm possess good structural stability and a high r1 relaxivity,and can achieve long-term DOX release.The cellular and animal experiments demonstrated that the DOX−PGH microspheres could facilitate targeted delivery of DOX to accelerate 4T1 cell death while reducing cancer cell metastasis due to the cooperative actions of long-term DOX-mediated chemotherapy and the fibrous microsphere-induced tumor anchoring to likely avoid primary tumor cell shedding,and render MR imaging of tumors during the treatment.The developed DOX−PGH microspheres may represent one of the updated local tumor chemotherapy formulations for improved tumor therapy with justified antitumor and anti-metastasis efficacy.

关键词： Electrospinning Porous fibrous microspheres tumor anchoring Local chemotherapy tumor metastasis

The progress and perspective of nanoparticle-enabled tumor metastasis treatment

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Acta Pharmaceutica Sinica B 2020年第11期10卷 2037-2053页

作者： Wei Zhang Fei Wang Chuan Hu Yang Zhou Huile Gao Jiang Hu Department of Orthopedics Sichuan Provincial People’s Hospital&Sichuan Academy of Medical Sciences&Affiliated Hospital of University of Electronic Science and TechnologyChengdu 610072China Key Laboratory of Drug Targeting and Drug Delivery System of the Education Ministry Sichuan Engineering Laboratory for Plant-Sourced Drug and Sichuan Research Center for Drug Precision Industrial TechnologyWest China School of Pharmacy Sichuan UniversityChengdu 610041China

As one of the most serious threats to human being,cancer is hard to be treated when metastasis happens.What’s worse,there are few identified targets of metastasis for drug development.Therefore,it is important to develop strategies to prevent metastasis or treat existed metastasis.This review focuses on the procedure of metastasis,and first summarizes the targeting delivery strategies,including primary tumor targeting drug delivery,tumor metastasis targeting drug delivery and hijacking circulation cells.Then,as a promising treatment,the application of immunotherapy in tumor metastasis treatment is introduced,and strategies that stimulating immune response are reviewed,including chemotherapy,photothermal therapy,photodynamic therapy,ferroptosis,sonodynamic therapy,and nanovaccines.Finally,the challenges and perspective about nanoparticle-enabled tumor metastasis treatment are discussed.

关键词： Nanoparticles tumor metastasis tumor targeting drug delivery Immunotherapy Photodynamic therapy Ferroptosis Nanovaccines Stimulating immune response

Gastrointestinal stromal tumor metastasis at the site of a totally implantable venous access port insertion:A rare case report

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World Journal of Clinical Cases 2020年第20期8卷 5007-5012页

作者： Xiao-Nan Yin Yuan Yin Jiang Wang Chao-Yong Shen Xin Chen Zhou Zhao Zhao-Lun Cai Bo Zhang Department of Gastrointestinal Surgery West China HospitalSichuan UniversityChengdu 610041Sichuan ProvinceChina

BACKGROUND The totally implantable venous access port(TIVAP)is an important device in patients for injecting blood products,parenteral nutrition or antineoplastic chemotherapy.Metastatic spread at the site of the insertion of a TIVAP is extremely rare.CASE SUMMARY We report the case of 33-year-old male with advanced gastrointestinal stromal tumor(GIST)who underwent radical tumor resection after neoadjuvant imatinib therapy.However,a solitary GIST metastasis at the site of a TIVAP insertion developed during adjuvant imatinib treatment.Mutational analysis showed secondary mutation in KIT exon 13(V564 A),which is resistant to imatinib treatment.To our knowledge,this is the first case report of a patient with advanced GIST developing GIST metastasis at the site of a TIVAP insertion.CONCLUSION This case highlights that when a patient with advanced,high metastatic GIST requires TIVAP insertion,we should realize that there is a risk of developing tumor metastasis at the site of a TIVAP insertion.

关键词： tumor metastasis Gastrointestinal stromal tumor Totally implantable venous access port Targeted therapy Mutational analysis Computed tomography Case report

P300/CBP-associated factor(PCAF)-mediated acetylation of Fascin at lysine 471 inhibits its actin-bundling activity and tumor metastasis in esophageal cancer

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Cancer Communications 2021年第12期41卷 1398-1416页

作者： Yin-Wei Cheng Fa-Min Zeng Da-Jia Li Shao-Hong Wang Jian-Zhong He Zhen-Chang Guo Ping-Juan Nie Zhi-Yong Wu Wen-Qi Shi Bing Wen Xiu-E Xu Lian-Di Liao Zhi-Mao Li Jian-Yi Wu Jun Zhan Hong-Quan Zhang Zhi-Jie Chang Kai Zhang Li-Yan Xu En-Min Li The Key Laboratory of Molecular Biology for High Cancer Incidence Coastal Chaoshan Area Department of Biochemistry and Molecular BiologyShantou University Medical CollegeShantouGuangdong 515041P.R.China Institute of Basic Medical Science Cancer Research CenterShantou University Medical CollegeShantouGuangdong 515041P.R.China Shantou Central Hospital Affiliated Shantou Hospital of Sun Yat-sen UniversityShantouGuangdong 515041P.R.China Guangdong Provincial Key Laboratory of Infectious Diseases and Molecular Immunopathology Institute of Oncologic PathologyShantou University Medical CollegeShantouGuangdong 515041P.R.China Tianjin Key Laboratory of Medical Epigenetics Department of Biochemistry and Molecular BiologySchool of Basic Medical SciencesTianjin Medical UniversityTianjin 300070P.R.China State Key Laboratory of Natural and Biomimetic Drugs Peking University Health Science CenterBeijing 100191P.R.China School of Medicine Tsinghua UniversityBeijing 100084P.R.China

Background:Fascin is crucial for cancer cell filopodium formation and tumor metastasis,and is functionally regulated by post-translational modifications.However,whether and how Fascin is regulated by acetylation remains unclear.This study explored the regulation of Fascin acetylation and its corresponding roles in filopodium formation and tumor metastasis.Methods:Immunoprecipitation and glutathione-S-transferase pull-down assays were performed to examine the interaction between Fascin and acetyltransferase P300/CBP-associated factor(PCAF),and immunofluorescence was used to investigate their colocalization.An in vitro acetylation assay was performed to identify Fascin acetylation sites by using mass spectrometry.A specific antibody against acetylated Fascin was generated and used to detect the PCAF-mediated Fascin acetylation in esophageal squamous cell carcinoma(ESCC)cells using Western blotting by overexpressing and knocking down PCAF expression.An in vitro cell migration assay was performed,and a xenograft model was established to study in vivo tumor metastasis.Live-cell imaging and fluorescence recovery after photobleaching were used to evaluate the function and dynamics of acetylated Fascin in filopodium formation.The clinical significance of acetylated Fascin and PCAF in ESCC was evaluated using immunohistochemistry.Results:Fascin directly interacted and colocalized with PCAF in the cytoplasm and was acetylated at lysine 471(K471)by PCAF.Using the specific antiAcK471-Fascin antibody,Fascin was found to be acetylated in ESCC cells,and the acetylation level was consequently increased after PCAF overexpression and decreased after PCAF knockdown.Functionally,Fascin-K471 acetylation markedly suppressed in vitro ESCC cell migration and in vivo tumor metastasis,whereas Fascin-K471 deacetylation exhibited a potent oncogenic function.Moreover,Fascin-K471 acetylation reduced filopodial length and density,and lifespan of ESCC cells,while its deacetylation produced the opposite effect.In the filipodium shaft,K471-acetyl

关键词： acetylation actin-bundling esophageal cancer fascin filopodium formation P300/CBPassociated factor(PCAF) tumor metastasis

General Survey of Traditional Chinese Medicine and Western Medicine Researches on tumor metastasis

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Chinese Journal of Integrated Traditional and Western Medicine 2006年第1期12卷 75-80页

作者：贺用和 Guang anmen Hospital China Academy of Chinese MedicalSciences Beijing （100053）

metastasis and recurrence of tumors is the chief cause of death for such patients. Therefore, researches on the mechanism of its metastasis, prevention and treatment are the focal points in the field of traditional Chinese medicine （TCM） and Western medicine （WM） at present. WM practitioners＂ study on tumor metastasis involved its occurrence and development including every detail and process, and now it even has developed into the molecular biological field. py is used as the main means, but the efficacy is not n treatment surgical operation and radio- chemotheratoo optimistic. In recent years, TOM, as part of the comprehensive therapy, has been gradually gaining attention of oncologists. Aimed at solving the difficult problems in metastasis of tumor, many TOM practitioners on the basis of syndrome differentiation have raised theories about the cause of tumor metastasis. On the basis of these theories, some TOM recipes against tumor metastasis have been developed to serve as an effective supplement to surgical operation, radio- and chemotherapy. The present article summarizes research results in recent years about the cause of formation of tumor and its metastasis by TOM and WM, so as to offer some theoretical clues to the study of tumors metastasis.

关键词： tumor metastasis study of traditional Chinese medicine and Western approach preventionand treatment of tumor metastasis

tumor Interstitial Fluid and Gastric Cancer metastasis:An Experimental Study to Verify the Hypothesis of "tumor-Phlegm Microenvironment"

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Chinese Journal of Integrative Medicine 2012年第5期18卷 350-358页

作者：孙大志矫健鹏巨大维叶敏张璇徐晶钰陆烨何金魏品康杨明会 Institute of Traditional Chinese Medicine Research Chinese People's Liberation Army General Hospital Department of Traditional Chinese Medicine Changzheng HospitalSecond Military Medical University Department of Traditional Chinese Medicine hangzheng HospitalSecond Military Medical University Department of Pathology Changzheng HospitalSecond Military Medical University

Objective： To extract tumor interstitial fluid （TIF） from MKN-45 gastric cancer which is similar to ＂muddy phlegm＂ in Chinese medicine and observe influences of MKN-45 tumor interstitial fluid （MKN-45 TIF） intervention on metastasis of gastric cancer and on the expressions of vascular endothelial growth factor （VEGF）, kinase insert domain containing receptor （KDR）, epithelial-cadherin （E-cad）, cyclooxygenase-2 （COX-2）, intercellular adhesion molecule-1 （ICAM-1） and telomerase genes and proteins in primary tumor tissue. Methods： An MKN-45 tumor-bearing model was established in 50 nude mice. The modeled animals were equally randomized to 5 groups： the simple tumor-bearing group （model group）, the normal saline （NS） via tail vein injection （i.v.） group （NS i.v. group）, MKN-45 TIF i.v. group （TIF i.v. group）, NS intraperitoneal injection （i.p.） group （NS i.p. group）, and MKN-45 TIF i.p. group （TIF i.p. group）. The TIF and NS intervention groups received injection （i.p. or i.v.） of MKN-45 TIF or NS twice a week, 0.2 mL at a time. After 8 weeks, the primary tumors were removed, weighed and HE stained to observe tumor metastasis. The primary tumor tissues were analyzed by immunohistochemistry and real-time quantitative PCR to detect expressions of VEGF, KDR, E-cad, COX-2, ICAM-1, and telomerase genes and proteins in different groups. Results： There were significant differences in tumor weight between TIF intervention groups and the model and NS intervention groups. tumor metastasis was observed in all 5 groups, but the tumor metastasis rate in TIF intervention groups was significantly higher than those in the model and NS intervention groups. The gene and protein expressions of gastric cancer-related factors VEGF, KDR, COX-2, ICAM-1 and telomerase were unregulated while the gene and protein expressions of E-cad were downregulated in TIF intervention groups. Conclusions： TIF promotes tumor growth, invasion and metastasis of gastric cancer. These findings provide preliminary experimental clues for verifying the hypothesis

关键词： tumor interstitial fluid gastric cancer tumor metastasis tumor metastasis-related genes and proteins

Effect of Juzentaihoto/Shi-Quan-Da-Bu-Tang on Malignant Progression and metastasis of tumor Cells

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World Journal of Traditional Chinese Medicine 2017年第4期3卷 26-45页

作者： lkuo Saiki Satoru Yokoyama Yoshihiro Hayakawa University of Toyama Division of Pathogenic Biochemistry Institute of Natural Medicine University of Toyama

A Japanese herbal(Kampo,汉方)medicine,十全大补汤(juzentaihoto/Shi-Quan-Da-Bu-Tang),is one of the nourishing agents, a so-called"补剂(Hozai/Bu-Ji)," that is used for improving disturbance and imbalances in the homeostatic condition of the body. This formulation is orally administered to patients in various weakened states, including postsurgery patients and patients with chronic illness, where it can alleviate general symptoms such as extreme fatigue, pale complexion, loss of appetite, dry or scaly skin, night sweating, and dryness of the mouth.Recently, juzentaihoto/Shi-Quan-Da-Bu-Tang has been shown to have a variety of biological activities, including activation of natural killer cells and macrophages, cytokine induction, antibody production, antitumor effects in combination with surgical excision or other drugs, and protection against the adverse effects of anticancer drugs and radiation, including immunosuppression and bone marrow toxicity. This article focuses on the antitumor and antimetastatic properties of some Kampo medicines and mainly describes the effects of juzentaihoto and its related formulations on tumor development, progression, and metastasis in vivo. We also discuss the inhibitory mechanism of action and the importance of the prescription and constituent crude drugs in determining the efficacy.

关键词： Epithelial-to-mesenchymal transition high-performance liquid chromatography pattern analysis Japanese herbal(Kampo) medicine juzentaihoto/Shi-Quan-Da-Bu-Tang macrophages malignant progression natural killer cells shimotsuto/Si-Wu-Tang tumor metastasis tumor vaccine