Shanghai Laiyi Center for Biopharmaceutical RandD

Shanghai, China

Shanghai Laiyi Center for Biopharmaceutical RandD

Shanghai, China
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Yang Z.,Shanghai JiaoTong University | Yang Z.,Shanghai Laiyi Center for Biopharmaceutical RandD | Ding J.,Nanjing Agricultural University | Ding K.,Institute of Medicinal Biotechnology Academy of Medical Science | And 4 more authors.
Phytochemistry Letters | Year: 2013

A novel dihydronaphthalenone, phomonaphthalenone A (1) was isolated from solid cultures of the endophytic fungus Phomopsis sp. HCCB04730, together with six known naphthoquinones (2-7). The structure of 1 was elucidated through spectroscopic and X-ray crystallographic analysis. Cytotoxic and anti-HIV activities of compounds 1-7 were also investigated. All compounds exhibited cytotoxic and anti-HIV activities. Compounds 1 and 7 showed moderate anti-HIV activities with IC50 values of 11.6 and 9.4 μg/mL, and relatively low cytotoxicity. Compounds 2, 4, and 5 showed significant cytotoxicity with IC50 values less than 4.7 μg/mL against A549, MDA-MB-231 and PANC-1 cell lines. © 2013 Phytochemical Society of Europe.

Li C.,East China University of Science and Technology | Li C.,Shanghai Laiyi Center for Biopharmaceutical RandD | Ge M.,Shanghai Laiyi Center for Biopharmaceutical RandD | Ge M.,Shanghai JiaoTong University | And 4 more authors.
Molecular and Cellular Biochemistry | Year: 2012

Oncogenic KRAS, an important target for antitumor therapy, contributes to pancreatic cancer tumorigenesis, progression and maintenance. However, intracellular compensation regulation can help cells to resist the targeted therapy. Gene knockdown method such as RNAi may help to understand this intracellular regulatory system and discover novel therapeutic approach. In this study, two stable transfected cell lines were constructed through lentivirus-mediated shRNA targeting KRAS of PANC-1 cells, to investigate cell response to the knockdown of KRAS. Human whole genome microarray was then used to compare the gene expression profile. As a result, ribosomal proteins L26 and L29 (RPL26 and RPL29) were dramatically upregulated by KRAS-shRNA specifically. To identify whether RPL26 or RPL29 was critical for PANC-1 cells, siRNAs against RPL26 and RPL29 were designed and transfected in vitro. The results showed that knockdown of RPL26 or RPL29 expression significantly suppressed cell proliferation, induced cell arrest at G0/G1 phase and enhanced cell apoptosis. Reactive oxygen species (ROS) assay indicated that silencing of RPL26 or RPL29 markedly decreased the intracellular ROS generation. Our findings imply that siRNA interference against RPL26 and RPL29 is of potential value for intervention of pancreatic cancer. © 2012 Springer Science+Business Media, LLC.

Li C.O.,Shanghai JiaoTong University | Li C.O.,Engineering Research Center for Cell Engineering and Therapeutic Antibody | Chen D.,Shanghai Institute of Pharmaceutical Industry | Luo M.,Shanghai Laiyi Center for Biopharmaceutical RandD | And 5 more authors.
Biotechnology Journal | Year: 2014

Pancreatic cancer remains a major unsolved health problem lacking a potent therapeutic option. Our previous studies showed that the ribosomal protein L39 (RPL39) gene was up-regulated after long-term silencing of oncogenic KRAS in pancreatic cancer PANC-1 cells, which indicated that RPL39 may be important for pancreatic cancer development and survival. In the current study, small interfering RNA (siRNA) targeting of the RPL39 gene was performed to determine the effects of the RPL39 gene on growth of pancreatic cancer PANC-1 and BxPC-3 cells in vitro and in vivo. Results from in vitro experiments showed that knockdown of RPL39 expression with RPL39-siRNA suppressed cell proliferation and specifically enhanced cell apoptosis significantly in both PANC-1 and BxPC-3 cells. The increase of caspase-8 activities and the loss of mitochondrial membrane potential after RPL39 silencing indicated that the RPL39 gene may be involved in caspase-8-related mitochondrial apoptosis. Further, treatment with the RPL39-siRNA inhibited the growth of a human pancreatic cancer xenograft in BALB/c nude mice, accompanied by a decreased expression of RPL39. In the xenograft tumors with injection of RPL39-siRNA, the expressions of Ki-67 and CD31 were significantly down-regulated, and apoptosis was markedly induced. Our findings suggested that siRNA against the RPL39 gene may be of value for gene therapy of pancreatic cancer. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Ruan L.,Shanghai JiaoTong University | Su D.,Shanghai JiaoTong University | Shao C.,Shanghai Laiyi Center for Biopharmaceutical RandD | Wang J.,Shanghai JiaoTong University | And 3 more authors.
Analyst | Year: 2015

In this paper, a sensitive and microscale method for drug screening is described using single molecule spectroscopy fluorescence correlation spectroscopy (FCS). The principle of this method is mainly based on the competition of candidate drugs to the fluorescent probe-target complexes and the excellent capacity of FCS for sensitively distinguishing the free fluorescent probes and the fluorescent probe-target complexes in solution. In this study, the screening of protein kinase inhibitors was used as a model, tyrosine-protein kinase ABL1 was used as a target and a known inhibitor dasatinib derivative labeled with a fluorescent dye was used as a fluorescent affinity probe. We firstly established the theoretical model of drug screening based on the binding process of fluorescent probes and targets, the competition of candidate drugs to the fluorescent probe-target complexes and FCS theory. Then, the dasatinib derivatives were synthesized and labeled with the fluorescent dye Alexa 488, and the binding and dissociation processes of Alexa 488-dasatinib and ABL1 were systematically investigated. The dissociation constant and the dissociation rate for the Alexa 488-dasatinib-ABL1 complex were determined. Finally, the established method was used to screen candidate drugs. The dissociation constants of ABL1 kinase to six known drugs for treating chronic myeloid leukemia (CML) were evaluated and the results obtained are well consistent with the reported values. Furthermore, a homemade chip with micro-wells was successfully utilized in FCS measurements as the carrier of samples, and the sample requirements were only 1-2 μL in this case. Our results demonstrated that the drug screening method described here is universal, sensitive and shows small sample and reagent quantity requirements. We believe that this method will become a high throughput platform for screening of small molecule drugs. This journal is © The Royal Society of Chemistry 2015.

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