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Correlation between Expression of DcR3 on Tumor Cells and Sensitivity to FasL

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Cellular & Molecular Immunology 2007年第6期4卷 455-460页

作者： Wenzhu Li Changgong Zhang Caixia Chen guohong zhuang Anti-Cancer Research Center Medical College Xiamen University 422 Siming South Road Xiamen Fujian 361005 China School of Life Science Xiamen University 422 Siming South Road Xiamen Fujian 361005 China

To investigate the correlation between sensitivity to Fas ligand （FasL） and expression level of decoy receptor 3 （DcR3） on tumor cell surface, Fas/DcR3 mRNA expression was detected by RT-PCR. Anti-DcR3 mAb was used to detect expression level of DcR3 on surface of tumor cells by flow cytometry. Caspase-8, caspase-9, caspase-3, Bcl-2 expressions were analyzed by Western blot, respectively. Sensitivity to apoptosis induced by FasL was determined by Annexin V apoptosis kit. The expressions of DcR3 on the surface of tumor cells from high to low were approximately 35.3% in BGC823 cells, and 21.6% in MCF-7 cells, respectively. The apoptotic rates induced by FasL from low to high were 15.6% in BGC823 cells, and 58.2% in MCF-7 cells, respectively. There was a significant correlation between the expression levels of DcR3 with FasL-inducing apoptosis. Cellular ＆ Molecular Immunology.

关键词： DcR3 FasL Fas apoptosis

TIPE-mediated up-regulation of MMP-9 promotes colorectal cancer invasion and metastasis through MKK-3/p38/NF-κB pro-oncogenic signaling pathway

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Signal Transduction and Targeted Therapy 2020年第1期5卷 1049-1051页

作者： Huiyu Chen Yuhan Ye Yan Yang Mengya Zhong Lei Gu Zhaopu Han Jinhua Qiu Zhongchen Liu Xingfeng Qiu guohong zhuang Cancer Research Center School of MedicineXiamen UniversityXiamenFujianChina Department of Pathology Zhongshan Hospital Affiliated to Xiamen UniversityXiamenFujianChina Department of General Surgery Shanghai 10th People’s Hospital Affiliated to Tongji UniversityShanghaiChina Department of Gastrointestinal Surgery Zhongshan Hospital Affiliated to Xiamen UniversityXiamenFujianChina Organ Transplantation Institute of Xiamen University Fujian Provincial Key Laboratory of Organ and Tissue RegenerationSchool of MedicineXiamen UniversityXiamenFujianChina

Dear Editor,Colorectal cancer(CRC)is the third most common malignant tumor in human,ranking third in cancer-related mortality.1 Most colon cancer patients die of metastasis.2 Intriguingly,the deregulation of tumor necrosis factorα‑induced protein 8(TIPE)has been shown to play a vital regulatory role in tumor cell growth,proliferation,invasion,and metastasis.3 TIPE is a kind of cytoplasmic protein of 23 kDa.A large number of studies have shown that TIPE is closely related to the development of colon cancer.4 In addition,decreased expression of TIPE was linked to down-regulation of matrix metallopeptidase-1(MMP-1),MMP-9,and vascular endothelial growth factor receptor-2 in breast cancer.

关键词： metastasis TIP p38

RGD-FasL Induces Apoptosis of Pituitary Adenoma Cells

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Cellular & Molecular Immunology 2008年第1期5卷 61-68页

作者： Lukui Chen guohong zhuang Wenzhu Li Yunsheng Liu Junqing Zhang Xinhua Tian Department of Neurosurgery Zhongshan Hospital Xiamen University Xiamen Fujian 361004 China Cancer Research Center Medical College Xiamen University Xiamen Fujian 361000 China School of Life Science Xiamen University Xiamen Fujian 361000 China Department of Neurosurgery Xiangya Hospital Zhongnan University Changsha Hunan China

This study was to investigate the cytotoxic effects on pituitary adenoma cell lines GH3/MMQ/AtT20 induced by RGD-FasL and the underlying mechanism. Fas/DcR3 mRNAs were detected by RT-PCR and their surface expressions were measured by flow cytometry. Cytotoxicity exerted by RGD-FasL on tumor cells was measured with MTT assay and the induced apoptosis was determined by agarose gel electrophoresis. The cell cycle and apoptosis was assessed by flow cytometry with PI staining. The expressions of caspase8/9/3, Bcl-2, RANKL and JNK2 were detected by Western blotting. Approximately 13.7% of GH3 cells, 25.5% of MMQ cells, 22.2% of AtT20 cells express Fas, while 23.9% of GH3 cells, 24.1% of MMQ cells, 4.6% of AtT20 cells express DcR3. The cytotoxic effects of FasL/RGD-FasL on tumor cells were all taken in a dose-dependent manner. Cell lines MMQ/AtT20 showed the same sensitivity to RGD-FasL as to FasL, while cell line GH3 was less sensitive to RGD-FasL. The cell cycle analysis indicated that RGD-FasL could inhibit cells in G0/G1 phase and G2/M phase. In MMQ and AtT20 cells treated with RGD-FasL, the AI was not significantly different from that treated with FasL, while in GH3 cells treated with RGD-FasL, the AI was lower than that treated with FasL. The expressions of caspase-8/9/3, RANKL and JNK2 were increased while that of Bcl-2 was decreased after treatment with RGD-FasL, suggesting that RGD-FasL induces apoptosis through caspase activation. We concluded that RGD-FasL could possibly be considered as a novel therapeutical candidate for the treatment of pituitary adenomas. Cellular ＆ Molecular Immunology.

关键词： RGD-FasL pituitary adenoma apoptosis

Induction of Tumor Cell Apoptosis via Fas/DR5

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Cellular & Molecular Immunology 2006年第6期3卷 467-471页

作者： Wenzhu Li Shengyu Wang Caixia Chen guohong zhuang School of Life Sciences Xiamen University Xiamen 361005 Fujian China Anti-Cancer Research Center Medical College Xiamen University Xiamen 361005 Fujian China

The apoptosis inducing effects on tumor cell lines MGC803, BEL7402 and HL60 by Fas ligand and anti-human DR5 monoclonal antibodies （anti-DR5 mAb） and the underlying mechanism was studied. Fas/DR5 mRNA was detected by RT-PCR. Cytotoxicity exerted by FasL/anti-DR5 mAb on tumor cell lines was measured by MTT assay and the induced apoptosis was determined by agarose gel electrophoresis. Flow cytometry was employed to analyze the mode of cell death. The mRNA expression of DR5 in MGC803 and BEL7402 cells after giving anti-DR5 mAb was up-regulated compared with control group, while it was down-regulated in HL60 cells in the same condition. The mRNA expression of Fas in HL60 was higher after giving FasL compared with control group, while it was lower in MGC803 and BEL7402. MGC803 and BEL7402 were sensitive to anti-DR5 mAb but partially to FasL, and HL60 was sensitive to FasL but less sensitive to anti-DR5 mAb. Apoptosis induced by Fas ligand and anti-DR5 mAb vary among tumor cell lines. The underlying mechanism may be relevant to Fas/DR5 mRNA expression, which was presented as the release of caspase-8 and Bcl-2.

关键词： FasL TRAIL death receptor apoptosis

RGD-FasL Induces Apoptosis in Hepatocellular Carcinoma

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Cellular & Molecular Immunology 2009年第4期6卷 285-293页

作者： Zhongchen Liu Juan Wang Ping Yin Jinhua Qiu Ruizhen Liu Wenzhu Li Xin Fan Xiaofeng Cheng Caixia Chen Jiakai Zhang guohong zhuang Anti-Cancer Research Center Medical College Xiamen University 422Siming South Road Xiamen 361005 China School of Life Science Xiamen University 422 Siming South RoadXiamen 361005 China Zhongshan Hospital Xiamen University Lakeside South 201-209 Xiamen361004 China These authors contributed equally to this work Anti-Cancer Research Center Medical College Xiamen University 422 Siming South Road Xiamen 361005 China

Despite impressive results obtained in animal models, the clinical use of Fas ligand （FasL） as an anticancer drug is limited by severe toxicity. Systemic toxicity of death ligands may be prevented by using genes encoding membrane-bound death ligands and by targeted transgene expression through either targeted transduction or targeted transcription. Selective induction of tumor cell death is a promising anticancer strategy. A fusion protein is created by fusing the extracellular domain of Fas ligand （FasL） to the peptide arginine-glycine-aspartic acid （RGD） that selectively targets avβ-integrins on tumor endothelial cells. The purpose of this study is to evaluate the effects of RGD-FasL on tumor growth and survival in a murine hepatocellular carcinoma （HCC） tumor model. Treatment with RGD-FasL displaying an obvious suppressive effect on the HCC tumor model as compared to that with FasL （p 〈 0.05） and resulted in a more additive effect on tumor growth delay in this model. RGD-FasL treatment significantly enhanced mouse survival and caused no toxic effect, such as weight loss, organ failure, or other treatment-related toxicities. Apoptosis was detected by flow cytometric analysis and TUNEL assays; those results also showed that RGD-FasL is a more potent inducer of cell apoptosis for H22 and H9101 cell lines than FasL （p 〈 0.05）. In conclusion, RGD-FasL appears to be a low-toxicity selective inducer of tumor cell death, which merits further investigation in preclinical and clinical studies. Furthermore, this approach offers a versatile technology for complexing target ligands with therapeutic recombinant proteins. To distinguish the anti-tumor effects of FasL in vivo, tumor and liver tissues were harvested to examine for evidence of necrotic cells, tumor cells, or apoptotic cells by Hematoxylin and eosin （H＆E） staining.

关键词： FasL RGD-FasL apoptosis tumor targeting

Combination of Human Fas （CD95/Apo-1） Ligand with Adriamycin Significantly Enhances the Efficacy of Antitumor Response

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Cellular & Molecular Immunology 2009年第3期6卷 167-174页

作者： Zhongchen Liu Ruizhen Liu Jinhua Qiu Ping Yin Fanghong Luo Jinhua Su Wenzhu Li Caixia Chen Xin Fan Jiakai Zhang guohong zhuang Anti-Cancer Research Center Medical College Xiamen University 422 Siming South Road Xiamen Fujian 361005 China Zhongshan Hospital Xiamen University 201-209 Lakeside South Xiamen Fujian 361004 China College of Life Science Xiamen University 422 Siming South Road Xiamen Fujian 361005 China These authors contributed equally to this work

The prognosis of hepatocellular carcinoma （HCC） is poor, even with the combined treatment of curative resection and adjuvant chemoradiotherapy. To solve this problem, many biologic therapies have been investigated. Fas ligand （FasL, CD95L） is mainly expressed in activated T lymphocytes and natural killer （NK） cells, and plays a central role in both cell-mediated immunity and immune downregulation. Several studies have shown that FasL is expressed in HCC. In the present report, we prepared recombinant human pET-22b（＋）/FasL protein and investigated the effect of FasL on HCC cells in vitro and on tumor growth in a murine HCC tumor model. The well-known cytotoxic chemotherapeutic reagent adriamycin （ADM） served as a control. We found that FasL effectively suppressed the viability of H22 tumor cells and significantly induced the apoptosis of H22 cells. The apoptotic levels of cells treated with FasL-ADM were significantly higher than those treated with FasL or ADM alone, and the FasL-ADM combination resulted in a more than additive effect on tumor growth delay in this model. The results suggested that combined treatment of FasL and other chemotherapeutic agents may be a new approach to improve the efficacy of chemotherapy for HCC.

关键词： hepatocellular carcinoma combination therapy FasL ADM apoptosis

常见免疫抑制剂与间充质干细胞的相互作用及研究进展

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中华实验外科杂志 2018年第6期35卷 1174-1176页

作者：李亚光庄国洪齐忠权厦门大学器官移植研究所 361102

目前临床常用的免疫抑制剂主要通过抑制机体免疫细胞功能而降低机体免疫反应强度，从而被广泛应用于器官移植领域及相关疾病治疗，然而其不良反应极大限制了其应用前景。近年来，多项研究表明，间充质干细胞（MSC）本身具有多元化的免... 详细信息

目前临床常用的免疫抑制剂主要通过抑制机体免疫细胞功能而降低机体免疫反应强度，从而被广泛应用于器官移植领域及相关疾病治疗，然而其不良反应极大限制了其应用前景。近年来，多项研究表明，间充质干细胞（MSC）本身具有多元化的免疫调节作用，在包括器官移植在内的多个医学领域中，如果联合应用MSC及经典免疫抑制剂，将能在最大限度发挥MSC免疫调节功效的同时，极大程度地降低免疫抑制剂的不良反应，因而，联合应用MSC及免疫抑制剂在医学领域具有极大的实用价值。现本文通过纵览近十年国内外相关领域研究，总结讨论MSC及临床常见免疫抑制剂之间的相互作用及联合作用效果极其可能机制，并做一综述。

关键词：间充质干细胞他克莫司西罗莫司来氟米特环孢A 霉酚酸酯硫唑嘌呤三氧化二砷

基于线上线下混合式教学模式培养医学生职业素养的医学免疫学课程思政教学实践

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中国免疫学杂志 2023年第6期39卷 1149-1151,1155页

作者：刘晓莉高丰光苟立新庄国洪(指导) 厦门大学医学院厦门361100 厦门大学生命科学学院厦门361100

为落实立德树人的根本教育任务,培养具备爱国精神、家国情怀、职业道德素养、医学人文精神、爱心奉献精神的医学人才,厦门大学医学院医学免疫学课程教学团队充分利用线上线下混合式教学模式的优势,开展了课程思政教学并取得了初步成效。

关键词：医学免疫学课程思政线上线下混合式教学改革

培养医学生自主学习能力和创新能力的医学免疫学线上线下混合式教学模式改革

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中国免疫学杂志 2023年第11期39卷 2402-2405页

作者：刘晓莉高丰光谢婷玉庄国洪(指导) 厦门大学医学院厦门361100

为探究基于“人卫慕课平台和云班课APP”的医学免疫学课程线上线下混合式教学模式改革对医学生自主学习能力和创新能力的影响,本文分析了临床医学专业学生医学免疫学课程线上自主学习情况、参与大学生创新训练计划项目情况、线上线下混... 详细信息

为探究基于“人卫慕课平台和云班课APP”的医学免疫学课程线上线下混合式教学模式改革对医学生自主学习能力和创新能力的影响,本文分析了临床医学专业学生医学免疫学课程线上自主学习情况、参与大学生创新训练计划项目情况、线上线下混合式教学模式满意度问卷调查结果。结果显示,线上线下混合式教学模式改革提升了医学生自主学习能力和创新能力。

关键词：医学免疫学混合式教学模式形成性评价教学改革

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