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Tributyrin inhibits human gastric cancer SGC-7901 cell growth by inducing apoptosis and DNA synthesis arrest

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World Journal of Gastroenterology 2003年第4期9卷 660-664页

作者： Jun Yan Yong-Hua Xu Lab of molecular and cellular Oncology and Lab of molecular Cell Biology,institute of Biochemistry and Cell Biology,Shanghai institutes for Biological Sciences,Chinese Academy of Sciences,Shanghai 200031,China Lab of molecular and cellular Oncology Institute of Biochemistry and Cell Biology Shanghai Institutes for Biological Sciences Chinese Academy of Sciences 320 Yue Yang Road Shanghai 200031 China.

AIM: To evaluate the effects of tributyrin, a pro-drug of natural butyrate and a neutral short-chain fatty acid triglyceride, on the growth inhibition of human gastric cancer SGC-7901 ***: Human gastric cancer SGC-7901 cells were exposed to tributyrin at 0.5, 1, 2, 5, 10 and 50 mmol·L-^1 for 24-72h. MTT assay was applied to detect the cell proliferation.[^3H]-TdR uptake was measured to determine DNA *** morphology was observed by electron microscopy and Hoechst-33258 staining. Flow cytometry and terminal deoxynudeotidyl transferase-mediated dUTP nick end labeling(TUNEL) assay were performed to detect tributyrin-triggered apoptosis. The expressions of PARP, Bcl-2 and Bax were examined by Western blot ***: Tributyrin could initiate growth inhibition of SGC-7901 cell in a dose-and time-dependent manner. [^3H]-TdR uptake by SGC-7901 cells was reduced to 33.6% after 48h treatment with 2mmol·L^-1 tributyrin, compared with the control (P<0.05). Apoptotic morphology was dell:ted by TUNEL assay. Flow cytometry revealed that tributyrin could induce apoptosis of SGC-7901 cells in dose-dependent manner. After 48 hours incubation with tributyrin at 2mmol·L^-1, the level of Bcl-2 protein was lowered, and the level of Bax protein was increased in SGC-7901, accompanied by PARP ***: Tributyrin could inhibit the growth of gastric cancer cells effectively in vitro by inhibiting DNA synthesis and inducing apoptosis, which was associated with the downregulated Bcl-2 expression and the up-regulated Bax expression. Therefore, tribublrin might be a promising chemopreventive and chemotherapeutic agent against human gastric carcinogenesis.

关键词：丁酸甘油酯胃癌细胞凋亡 DNA合成抑制 SGC-7901细胞系化学疗法

Perspectives on the origin of microfilaments, microtubules, the relevant chaperonin system and cytoskeletal motors- a commentary on the spiro chaete origin of flagella

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Cell Research 2003年第4期13卷 219-227页

作者： JING YAN LI, CHUAN FEN WULaboratory of cellular and molecular Evolution, Kunming institute of Zoology, Chinese Academy of Sciences, Kunming, Yunnan 650223, China Department of molecular Genetics, M. D. Anderson Cancer Center, The University of Texas, Houston, TX 77030, USA Laboratory of cellular and molecular Evolution Kunming Institute of Zoology Chinese Academy of Sciences Kunming China

The origin of cytoskeleton and the origin of relevant intracellular transportation system are big problems for understanding the emergence of eukaryotic cells. The present article summarized relevant information of evidences and molecular traces on the origin of actin, tubulin, the chaperonin system for folding them, myosins, kinesins, axonemal dyneins and cytoplasmic dyneins. On this basis the authors proposed a series of works, which should be done in the future, and indicated the ways for reaching the targets. These targets are mainly: 1) the reconstruction of evolutionary path from MreB protein of archaeal ancestor of eukaryotic cells to typical actin; 2) the finding of the MreB or MreB-related proteins in crenarchaea and using them to examine J. A. Lake’s hypothesis on the origin of eukaryote from 'eocytes' (crenarchaea); 3) the examinations of the existence and distribution of cytoskeleton made of MreB-related protein within coccoid archaea, especially in amoeboid archaeon Thermoplasm acidophilum;

关键词： origin actin tubulin motor proteins Bagella and cilia spirochaete hypothesis.

Deregulated c-myc expression in quiescent CHO cellsinduces target gene transcription and subsequent apoptotic phenotype

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Cell Research 1999年第4期9卷 305-314页

作者： FANG CHANG MING CAN SHI YONG HUA XU(Laboratory of molecular and cellular Oncology, Shanghai)(institute of Cell Biology, Chinese Academy of Sciences,320 Yue Yang Road, Shanghai 200031, China) Laboratory of molecular and cellular Oncology Shanghai Institute of Cell Biology Chinese Academy of Sciences Shanghai China

INTRODUCTIONThec-mycproto--oncogene,thecellularhomologueofthegenebornbytheretrovirusMC29,isresponsibleforchickenleukemia[1],anditoriginallygotitsnamefortheabilitytocausemyelocytomatosisinsusceptibleanimalsandculturedc... 详细信息

关键词： c-myc CHO cell line apoptosis c-myctarget genes.

Down-regulated expression of atypical PKC-binding domain deleted asip isoforms in human hepatocellular carcinomas

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Cell Research 2001年第3期11卷 223-229页

作者： FANG CHANG MINC, YONG HUA XU Laboratory of molecular and cellular Oncology, institute of Biochemistry and Cell Biology, Shanghai institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China Laboratory of molecular and cellular Oncology Institute of Biochemistry and Cell Biology Shanghai Institutes for Biological Sciences Chinese Academy of Sciences Shanghai China

Asip is a mammalian homologue of polarity protein Par-3 of Caenorhabditis elegans and Bazooka of Drosophila melanogaster. Asip/Par-3/Bazooka are PDZ-motif containing proteins that localize asymmetrically to the cell periphery and play a pivotal role in cell polarity and asymmetric cell division. In the present study, we have cloned human asip cDNA and its splicing variants by 5’-RACE and RT-PCR using candidate human EST clones which have a high homology to rat asip cDNA. The full-length cDNA of human asip encodes a 1,353 aa protein exhibiting 88% similarity to the rat one. Human asip is a single copy gene consisting of at least 26 exons and localizing in human chromosome 10, band p11.2, with some extraordinarily long introns. All exon/intron boundary nucleotides conform to the "gt-ag" rule. Three main transcripts were detected by Northern blot analysis, and at least five variants, from alternative splicing and polyadenylation, have been identified by RT-PCR and liver cDNA library screening. Exon 17b deleted asip mRNAs expressed ubiquitously in normal human tissues, including liver, on RT-PCR analysis. However, they were absent from most human liver cancer cell lines examined. More interestingly, the expression of exon 1 7b deleted variants was down regulated in 52.6% (10/19) clinic specimens of human hepatocellular carcinomas (HCCs), compared with the surrounding nontumorous liver tissues from the same patients. The presence of various splicing transcripts, the variation of their distribution among different tissues and cells, and their differential expressions in human HCCs suggest that human Asip isoforms may function in different context.

关键词： Alternative splicing and polyadenylation A sip/Par-3/Bazooka PDZ-motif protein Polarity protein hepatocellular carcinomas.

A New Combination of Mutated loxPs in a Vector for Construction of Phage Antibody Libraries

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Acta Biochimica et Biophysica Sinica 2005年第7期37卷 495-500页

作者： Yu GAN~(1,2) Xin-Tai ZHAO~2 1 Shanghai Medical College,Fudan University,Shanghai 200032,China 2 Laboratory for cellular and molecular Immunology,Cancer institute,Shanghai Jiaotong University,Shanghai 200032,China Shanghai Medical College Fudan UniversityShanghai 200032 China Laboratory for cellular and molecular Immunology Cancer Institute Shanghai Jiaotong UniversityShanghai 200032 China

In the construction of large antibody libraries by in vivo recombination,two non-homogeneousloxP sites are required for the exchange of V genes between phagemids to create many new *** mutated loxP511 was designed not to recombine with the wild-type loxP （loxPwt） in early studies anda combination of the two has been used to construct antibody *** recent reports have shown thatrecombination occurs between loxPwt and *** suggests that the combinational use of loxP511and loxPwt might lead to the loss of the V gene diversity of antibody ***,it is necessary tofind a new combination of loxPs to avoid the excision recombination in the antibody *** this study,we found that the excision recombination between loxP511 and loxP2272,another mutated loxP sequence,was undetectable within one phagemid,while the excision recombination between loxP511 and loxPwtoccurred at a frequency of 40%.higher than that reported ***,the in vivo recombinationof different phagemids with loxP511 and loxP2272 showed that the V gene exchange was efficiently mediatedto produce new *** was concluded that the loxP511 and loxP2272 combination wasmore favorable for reducing the excision recombination and constructing large phage antibody libraries withhigh diversity.

关键词： mutated loxP excision recombination phage antibody library

Melanocortin-1 receptor gene variants in four Chinese ethnic populations

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Cell Research 2001年第1期11卷 81-84页

作者： SHI PENG, XUE MEI LU, HUAI RONG LUO, JIN-GONG XIANG-YU, YA PING ZHANG (Laboratory of cellular and molecular Evolution, Kunming institute of Zoology, the Chinese Academy of Sciences, Kunming 650223, China) Laboratory of cellular and molecular Evolution Kunming Institute of Zoology the Chinese Academy of Sciences Kunming China

There is strong relationship between melanocortin-1 receptor (MCIR) gene variants and human hair color and skin type. Based on a sequencing study of MC1R gene in 50 individuals from the Uygur, Tibetan, Wa and Dai ethnic populations, we discuss the occurrence of 7 mc1r variants consisting of 5 nonsynonymous sites (Val60Leu, Arg67Gln, Val92Met, Arg163Gln and Ala299Val) and 2 synonymous sites (C414T and A942G), among which C414T and Ala299Val were reported for the first time. Confirmation and analysis were the made of 122 individuals at three common point mutations (Val92Met, Arg163Gln, A942G) using PCR-SSCP. The frequency of Arg163Gln variant varies in the four ethnic populations, with percentage of 40%, 85.0%, 66. 2% and 72.7%, respectively, while those of Val92Met and A942G are roughly similar in these four populations. The different environments, migration and admixture of various ethnic groups in China might have impact on the observed frequency of Arg163Gln.

关键词： MC1R gene ethnic populations nonsynonymous site synonymous site.

Dynamics of RNA with A6 bulge loop

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Chinese Science Bulletin 2002年第12期47卷 1003-1006页

作者： LIANG Chongrong & LIU CiquanKey Laboratory of cellular & molecular Evolution, Kunming institute of Zoology, Chinese Academy of Sciences, Kunming 650223, China Biology Department, Jinan University, Guangzhou 510630, China Key Laboratory of cellular & molecular Evolution Kunming Institute of Zoology Chinese Academy of Sciences Kunming China Biology Department Jinan University Guangzhou China

In order to understand the behavior of RNAs with large bulges in solution, molecular dynamics was performed on the RNA molecule in water with A6 bulge. The result of simulation showed that nonstacked conformation is the main conformation in large bulges, and the backbone of large bulge is of great conformational flexibility, but bulges-induced bends are relatively rigid. The fluctuation in bulge has little influence on the bend angle of RNAs.

关键词： RNA large bulge conformation bend angle.

Fractals of Protein Backbone Structures

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生物数学学报 1997年第S1期12卷 385-392页

作者： Huang Jingfei Liu Ciquan(Laboratory of cellular and molecular Evolution,Kunming institute of Zoology,The Chinese Academy of Sciences,Kunming,Yunnan 650223)

Ths paper，based on the principles of geometric self-similarity of fractal theory and some research results of rotein chemistry，improved the method of comput－ing protein fractal dimensions，and computed fractal dimensions of some protein back bone，secondary and assumed folding *** relationship between protein back-bone strucrural fractal dimensions and its spatial structures was *** results indicated that protein backbone fractal dimensions not only have a close relation with protein secondary structure，but also with its *** addition，the folding of protein Polypeptide chains in 3-D space may be similar to the other macromolecular chain be haviour described by the self-avoiding walks（SAW）model．

关键词： Fractal dimension protein backbone structure secondary structure folding

Synthesis of 2,6-Dimethoxyhydroquinone-3-mercaptoacetyl-peptide-chlorambucil Conjugates

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Chinese Chemical Letters 2000年第10期11卷 879-882页

作者： Yu Fei SONG (institute of molecular Science, Shanxi University, Taiyuan 030006) institute of molecular Science Shanxi University Taiyuan 030006 China

This paper reports a continous study of the use of short chain peptides as carriers of a potential antitumor agents: 2,6-dimethoxyhydroquinone-3-mercaptoacetic acid (DMQ-MA). In an effort to carry out anti-cancer drug design, we synthesized another two new DMQ-MA-peptide-chlorambucil (CRB) derivatives: DMQ-MA-Lys(CRB)-Arg-OMe, DMQ-MA-Lys(DMQ-MA)Lys(CRB)-Arg-OMe. These peptide-chlorambucil conjugates were synthesized by coupling protected amino acids in solution and the next conjugation was achieved by reacting with pentafluorophenyl ester of DMQ-MA in DMF. The CRB in side chain was coupled by deblocking the lysyl-carbobenzyloxy protecting group Z and then reacting with the pentafluorophenyl ester of chlorambucil (CRB). Further study on cytotoxicity, DNA binding, and sequence specificity of DNA alkylation of these two new conjugates are investigating.

关键词： 2.6-dimethoxyhydroquinone-3-mercaptoacetic acid chlorambucil peptide