曲显俊
新药药理及抗癌药物药理学,实验肿瘤学,活性化合物筛选及临床前安全性评价等。
个性化签名
- 姓名:曲显俊
- 目前身份:
- 担任导师情况:
- 学位:
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学术头衔:
博士生导师
- 职称:-
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学科领域:
药物化学
- 研究兴趣:新药药理及抗癌药物药理学,实验肿瘤学,活性化合物筛选及临床前安全性评价等。
曲显俊,男,1961年10月出生,山东莱州人。山东大学药学院新药药理研究所所长,中日药物筛选中心主任。
[研究方向] 新药药理及抗癌药物药理学,实验肿瘤学,活性化合物筛选及临床前安全性评价等。
[科研项目]
1. 国家自然基金项目“以Pgp为靶点的喹喔啉酮化合物对肿瘤细胞耐药性的逆转作用研究”,首位承担人。时间: 2007-2009年。
2. 国家自然基金项目“吡咯烷类MMP抑制剂抗癌作用机制及构效关系研究”,首位承担人,30472038。时间: 2005-2007年。
3. 以MMP-2,9为靶点的吡咯烷类化合物抗肿瘤转移作用研究,山东省卫生系统第三中青年重点科技人才资助计划1020。
[获奖情况]
2006年度山东大学校长奖学金
2006年度英国皇家学会科研奖励
山东省卫生系统第三批中青年重点科技人才1020奖励
[学习和工作经历]
2004.03—至今,山东大学药学院新药药理研究所,教授。其中,2005年12月-2006年8月,东京大学医学部客员研究员。2007年1月-3月,英国Bath大学药学与药理学系访问学者。
2001.01—2004.02,澳大利亚新南威尔斯大学王子医院博士后研究员。
2000.02—2000.05,日本东海大学工学部客员研究员。
1983.07—2000.02,山东省医学科学院药物研究所,分别任职实习研究员、助理研究员,副研究员,研究员。其中1986年6月—1989年6月,山东省医学科学院硕士研究生,医学硕士学位。
1978.10—1983.07,青岛医学院医疗系学习,医学学士学位。
[研究简况]
从事药理学教学与科研工作,在实验肿瘤学、分子药理学及新药药理研究方面,进行肿瘤发病机制、诊断方法及活性化合物筛选研究工作,为寻找新药提供理论基础和研究途径。开展的主要工作:抗肿瘤药物活性筛选、作用机制及新药临床前安全性评价。先后承担抗癌新药-奈达铂的研究;抗癌新药-替加氟氧嗪吉美研究;小檗碱对耐药性白血病细胞逆转作用研究;姜黄素对人肿瘤细胞端粒酶活性作用研究等。1999年进入日本东海大学工学部从事糖蛋白结构研究,2001年至2003年,澳大利亚新南威尔斯大学王子医院肿瘤研究中心,进行干扰素对结肠癌和膀胱癌细胞生长因子受体(EGFR)调节作用研究。2005年和2006年连续获得国家自然基金资助,研究MMPs和APN抑制剂抗肿瘤转移作用和肿瘤细胞耐药机制及其逆转剂作用研究。2005年12月进入东京大学医学部大学院从事合作研究原发性肝癌转移机制。2006年9月,与英国巴斯大学Steve Award教授共同获得英国皇家学会资助,研究吡咯烷类MMPs抑制剂对肿瘤转移的抑制作用。
[学术任职]
中国药理学会应用药理委员会和海洋药物委员会委员,中华预防肿瘤学杂志编委,日本BioScience Trends杂志编委,日本国际生命科学交流促进协会理事等。
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6
曲显俊, XIANJUN QU, YUNXIA YUAN, WENFANG XU, MINGHUI CHEN, SHUXIANG CUI, HONG MENG, YAN LI, MASATOSHI MAKUUCHI, MUNEHIRO NAKATA, and WEI TANG,
ANTICANCER RESEARCH 26: 3573-3578(2006),-0001,():
-1年11月30日
Abstract. Background: LY52 is a caffeoyl pyrrolidine derivative designed to fit and extend into the active pocket of matrix metalloproteinase (MMP). In this study, the effects of LY52 on MMP-2 and MMP-9 activities and tumor invasion and metastasis were examined. Materials and Methods: MMP expression in SKOV3 cells was analyzed by gelatin zymography. The anti-invasion and anti-metastasis abilities of LY52 were evaluated with penetration of SKOV3 cells through Matrigelcoated membrane in vitro and pulmonary metastasis of Lewis lung carcinoma in mice, respectively. Results: LY52 significantly blocked the proteolytic activity of gelatinase. Gelatin zymography revealed that MMP-2 and MMP-9 expressions in SKOV3 cells were reduced in the presence of LY52. LY52 also suppressed SKOV3 cell invasion in vitro. Furthermore, a significant inhibition of pulmonary metastasis of Lewis lung carcinoma cells was observed in LY52-administrated mice. Conclusion: LY52 might suppress invasion and metastasis of carcinoma cells via inhibition of MMP-2 and MMP-9 proteolytic activities.
LY52,, caffeoyl pyrrolidine derivative,, matrix metalloproteinase,, tumor invasion,, metastasis.,
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【期刊论文】Induction of Apoptosis in Human Hepatocellular Carcinoma Cells by Synthetic Antineoplaston A10
曲显俊, XIAN-JUN QU, SHU-XIANG CUI, ZHIGANG TIAN, XUN LI, MING-HUI CHEN, WEN-FANG XU, YOSHINORI INAGAKI, , YING-BING DENG, MASATOSHI MAKUUCHI, MUNEHIRO NAKATA, and WEI TANG
ANTICANCER RESEARCH 27: 2427-2432(2007),-0001,():
-1年11月30日
Antineoplaston A10 (3-phenylacetylamino-2,6-piperidinedion) is a naturally occurring substance and was the first antineoplaston in the human body to be chemically identified. The effect of antineoplaston A10 on human hepatocellular carcinoma cell lines HepG2 and HLE has been examined. Antineoplaston A10 displayed anti-proliferative action inhibiting cell growth in a dose-and time-dependent manner in vitro as measured by 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide (MTT) and clonogenic assays. Incubation with antineoplaston A10 for 48 h induced apoptotic events such as a typical apoptotic morphology, formation of a characteristic ladder pattern of DNA migration and accumulation of sub-G1 phase cells. Next, hepatoma xenografts in nude mice were employed to study the antitumor effects of antineoplaston A10 in vivo. Oral administration of antineoplaston A10 delayed the growth of HepG2 and HLE cells in the mice without a reduction in body weight. A higher proportion of apoptotic cells in xenografts was observed by means of terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling (TUNEL) staining. In addition, the level of expression of apoptotic marker p53 increased while that of anti-apoptotic protein bcl-2 decreased, as evaluated with immunohistochemical staining in the xenografts. These results suggested that antineoplaston A10 may inhibit the growth of human hepatoma cells through the induction of apoptosis.
Antineoplaston A10,, hepatocellular carcinoma,, apoptosis.,
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曲显俊, Jian Liua, b, Xun Lia, Yan-na Chenga, Shu-xiang Cuic, Ming-hui Chena, Wen-fang Xua, Zhi-gang Tiana, Masatoshi Makuuchid, Wei Tanga, d, Xian-jun Qua
European Journal of Pharmacology 574(2007)1-7,-0001,():
-1年11月30日
N3-o-toluyl-fluorouracil (TFU), the pro-drug of 5-fluorouracil (5-FU), is the metabolite of N1-acetyl-N3-o-toluyl-fluorouracil (atofluding). We aimed to evaluate the efficacy of TFU as a precursor of 5-FU on the growth inhibition of human gastric carcinoma cell lines SGC-7901 and MKN-45. Growth of SGC-7901 and MKN-45 cells was remarkably suppressed by treatment with TFU in the presence of liver microsomal enzymes in vitro, suggesting that TFU may be converted to 5-FU by the enzymes. Similar treatment of TFU induced apoptosis of the cells, which was deduced from typical apoptotic features such as morphology, the formation of characteristic ladder pattern of DNAmigration and the accumulation of sub-G1 phase. Cancer cells xenografts in nude mice were employed to evaluate the efficacy of TFU in vivo. Growth of human gastric carcinoma cells was significantly delayed by oral administration of TFU with low side effects. Apoptosis in xenografts was also observed by means of TUNEL staining method. These results suggest that the treatment of TFU in the presence of liver microsomal enzymes and the oral administration of TFU in mice induced anti-proliferation and apoptosis in gastric carcinoma cells. This suggests that TFU may be a promising pro-drug of 5-FU for cancer treatments.
N3-o-toluyl-fluorouracil (, TFU), , 5-fluorouracil, Gastric carcinoma, Growth inhibition, Apoptosis
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曲显俊, Subo Wanga, Yanna Chengb, Fengshan Wangb, Lirui Sunb, Chunhui Liub, Guanjun Chena, Yuhua Lib, S.G. Ward, c, Xianjun Qub, *
Biomedicine & Pharmacotherapy 62(2008)297-302,-0001,():
-1年11月30日
SIP-SII is the sulfated S. maindroni ink polysaccharide (SIP) isolated from cuttlefish Sepiella maindroni. SIP-SII weakly inhibited tumor cell growth without cytotoxicity in vitro assay. Herein, we examined the effects of SIP-SII on the expression of matrix metalloproteinase MMP-2 and MMP-9 as well as tumor cell invasion and migration. SIP-SII (0.8e500 mg/ml) significantly decreased the expression of MMP-2 activity in human ovarian carcinoma cells SKOV3 as evidenced by the gelatin zymography analysis. No significant decrease of MMP-9 was detected in the cell line after SIP-SII treatment. The expression of MMP-2 was also evaluated using Western blot analysis. The results showed that SIP-SII inhibited the expression of MMP-2 in SKOV3 and human umbilical vein vascular endothelial cells ECV304 after 24 h incubation. Furthermore, the activity of invasion and migration of SKOV3 and ECV304 cells were measured. SIP-SII displayed an inhibitory effect on the penetration of SKOV3 cells through Matrigel-coated membrane in transwell chamber. A significant inhibition of ECV304 cell migration was observed in the presence of SIP-SII. These results suggest that SIP-SII might suppress invasion and migration of carcinoma cells via inhibition of MMP-2 proteolytic activity.
S., maindroni ink polysaccharide (, SIP), , Sulfated polysaccharide (, SIP-SII), , Matrix metalloproteinases, MMP-2, Tumor invasion, Migration
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曲显俊, Minghui Chen, Shuxiang Cui, Yanna Cheng, Lirui Sun, Qianbin Li, Wenfang Xu, S.G Ward, Wei Tang, , Xianjun Qu, *
,-0001,():
-1年11月30日
Matrix metalloproteinase-2 (MMP-2) and MMP-9 have been associated with the ability of tumor cells to metastasize due to their capacity to degrade type IV collagen, the main component of basement membrane, and to their elevated expression in malignant tumors. (S)-methyl 6-(benzyloxycarbonylamino)-2-(2-(S)-2,6-dioxo-3-(3,4,5-trimethoxybenzamido) piperidin-1-yl)acetamido)hexanoate (CH1104I) is a galloyl cyclic-imide derivative designed to fit and extend into the S1' active pocket of MMP-2 and MMP-9. We aimed to evaluate the efficacy of CH1104I as a candidate compound for anti-invasion and anti-metastasis of tumor cells. CH1104I significantly blocked gelatinase activity as evidenced by a decrease in the degradation of succinylated gelatin. Gelatin zymography analysis showed that the compound (7-210 μM) inhibited the activity of MMP-2 and MMP-9 produced by human ovarian carcinoma SKOV3 cells. Inhibition of MMP-2 and MMP-9 expression was also observed using the assays of immunocytochemical staining and Western blot analysis. The results showed that CH1104I suppressed the expression of zymogens and active-MMP-2 and MMP-9. The effects of CH1104I on invasion and migration of SKOV3 cells were then measured. CH1104I displayed an inhibitory effect on the penetration of SKOV3 cells through Matrigel-coated membrane in transwell chamber. Furthermore, Lewis lung carcinoma (LLC) model was employed to evaluate the efficacy of CH1104I in vivo. A significant inhibition of pulmonary metastasis of carcinoma cells was observed in CH1104I-administrated mice (25-100 mg/kg). These results suggest that CH1104I is a potential MMP-2 and MMP-9 inhibitor that may effectively suppress tumor invasion and metastasis.
Galloyl cyclic-imide derivative,, CH1104I,, MMP-2,, MMP-9,, Invasion and metastasis
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曲显俊, Fu-Jun Gaoa, , Shu-Xiang Cuib, Ming-Hui Chena, Yan-Na Chenga, Li-Rui Suna, S.G. Wardc, Norihiro Kokudod, Wei Tanga, d, Xian-Jun Qua
Life Sciences 83(2008)815-820,-0001,():
-1年11月30日
Aims: Des-γ-carboxyl prothrombin (DCP) is a serum protein produced by hepatocellular carcinoma (HCC) cells. The aim of this study was to evaluate the angiogenic activity of DCP in HCC cells. Main methods: The proliferation of HCC cells was measured by 3-[4, 5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide (MTT) assay. The growth of HCC cells was also evaluated in vivo by using the xenografts in nude mice. The enzyme-linked immunosorbent assay (ELISA) was employed to measure the levels of angiogenic factors in supernatant of cell culture. The expression of angiogenic factors was examined by Western blot analysis and immunohistochemical staining. Key findings: DCP displayed the stimulation of HCC cell growth in a dose (5–80 ng/ml) and time (24–96 h) dependent manner. The increase of cell growth was also observed in nude mice bearing well-established, palpable HepG2 and SMMC-7721 xenografts after 2 weeks administration of DCP. HCC cell growth was accompanied by the elevated levels of angiogenic factors. The levels of vascular endothelial growth factor (VEGF), transforming growth factor-alpha (TGF-α) and basic fibroblast growth factor (bFGF) in supernatant of SMMC-7721 cells were increased from 47, 126, and 60 pg/106 cells/24 h to 400, 208, and 298 pg/106 cells/ 24 h, respectively, after 72 h incubation with 80 ng/ml of DCP. The results of Western blot analysis and immunohistochemical staining of HCC xenografts also showed the significant increase of VEGF, TGF-α, and bFGF in HCC cells.
Des-gamma-carboxy prothrombin (, DCP), Hepatocellular carcinoma cells (, HCC), HepG2 SMMC-7721 Angiogenic factors
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