-
Yong Fang,
Yi Hu,
Peng Wu,
Beibei Wang,
Yuan Tian,
Xi Xia,
Qinghua Zhang,
Tong Chen, Xuefeng Jiang,
Quanfu Ma,
Gang Xu,
Shixuan Wang,
Jianfeng Zhou,
Ding Ma,
Li Meng
[show abstract]
[hide abstract]
ABSTRACT: Histone deacetylase inhibitors and proteasome inhibitor are all emerging as new classes of anticancer agents. We chose TSA and PS-341 to identify whether they have a synergistic efficacy on human ovarian cancer cells. After incubated with 500 nM TSA or/and 40 nM PS-341, we found that combined groups resulted in a striking increase of apoptosis and G2/M blocking rates, no matter in A2780, cisplatin-sensitive ovarian cancer cell line OV2008 or its resistant variant C13*. This demonstrated that TSA interacted synergistically with PS-341, which raised the possibility that combined the two drugs may represent a novel strategy in ovarian cancer.
Cancer Investigation 02/2011; 29(4):247-52. · 1.85 Impact Factor
-
Shuangmei Ye,
Xing Hao,
Ting Zhou,
Mingfu Wu,
Juncheng Wei,
Yongjun Wang,
Li Zhou, Xuefeng Jiang,
Li Ji,
Yin Chen,
Lanying You,
Yiqun Zhang,
Gang Xu,
Jianfeng Zhou,
Ding Ma,
Shixuan Wang
[show abstract]
[hide abstract]
ABSTRACT: Elevated Plexin-B1 expression has been found in diverse human cancers and in non-neoplastic tissues, and it mediates diverse biological and pathological activities. However, whether or not Plexin-B1 expression is involved in human ovarian tumors remains unclear. In the present study, Plexin-B1 expression was explored in benign and malignant human ovarian tumor tissues. In addition, the impact of Plexin-B1 expression on ovarian cancer cell proliferation, migration and invasion were investigated in vitro.
Plexin-B1 expression was analyzed in normal and benign ovarian tissues and serous ovarian tumors (both borderline and malignant) by immunohistochemical staining, as well as in four human ovarian cancer cell lines (A2780, C13*, SKOV3, and OV2008) by RT-PCR and western blot analyses. Furthermore, endogenous Plexin-B1 expression was suppressed by Plexin-B1 siRNA in SKOV3 cells, which overexpress Plexin-B1. Protein levels of Plexin-B1, AKT and AKTSer473 were examined by western blot analysis. Cell proliferation, migration and invasion were measured with MTT, wound healing and boyden chamber assays, respectively, and the cytoskeleton was monitored via F-actin staining.
Expression levels of Plexin-B1 protein were significantly higher in serous ovarian carcinomas than in normal ovaries or benign ovarian neoplasms, and in the former, Plexin-B1 expression was positively correlated with lymphatic metastasis, and the membrane and cytoplasm of cancer cells stained positively. SKOV3 cells displayed the highest Plexin-B1 expression at both the mRNA and protein levels among the four tested human ovarian cancer cell lines and was selected as a cell model for further in vitro experiments. Plexin-B1 siRNA significantly suppressed phosphorylation of AKT at Ser473 in SKOV3 cells, but it did not alter total AKT expression. In addition, silencing of Plexin-B1 in SKOV3 cells inhibited cell migration and invasion and reorganized the cytoskeleton, whereas cell proliferation was not affected.
Plexin-B1 expression correlates with malignant phenotypes of serous ovarian tumors, probably via phosphorylation of AKT at Ser473, suggesting that Plexin-B1 might be a useful biomarker and/or a novel therapeutic target.
BMC Cancer 11/2010; 10:611. · 3.01 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: The purpose of this study was to pool information in epithelial ovarian cancer by combining studies using Affymetrix expression microarray datasets made at different laboratories to identify novel biomarkers. Epithelial microarray expression information across laboratories was screened and combined after preprocessing raw microarray data, then ANOVA and unpaired T test statistical analysis was performed for identifying differentially expressed genes (DEGs), followed by clustering and pathway analysis for these DEGs. In this work, we performed a combination analysis on microarrays from three different laboratories using gene expression data on ovarian cancer and obtained a list of differential expression profiles identified as potential candidate in aggressiveness of ovarian cancer. The clustering and pathway analysis explored the different molecular basis of different ovarian cancer stages and potential important regulatory pathways in ovarian cancer development. Our results showed that combination of microarray data from different laboratories in the same platforms may overcome biases derived from probe design and technical features, thereby accelerating the identification of trustworthy DEGs, and demonstrating the advantage of integrative analysis in gene expression studies on epithelial ovarian cancer research.
Journal of Huazhong University of Science and Technology 06/2010; 30(3):354-9. · 0.38 Impact Factor
-
Zhiqiang Han,
Zhenya Hong,
Caihong Chen,
Qinglei Gao,
Danfeng Luo,
Yong Fang,
Yang Cao,
Tao Zhu, Xuefeng Jiang,
Quanfu Ma,
Wei Li,
Lingfei Han,
Daowen Wang,
Gang Xu,
Shixuan Wang,
Li Meng,
Jianfeng Zhou,
Ding Ma
[show abstract]
[hide abstract]
ABSTRACT: Tumor cells acquire the ability to proliferate uncontrollably, resist apoptosis, sustain angiogenesis and evade immune surveillance. Signal transducer and activator of transcription (STAT) 3 regulates all of these processes in a surprisingly large number of human cancers. Consequently, the STAT3 protein is emerging as an ideal target for cancer therapy. This paper reports the generation of an oncolytic adenovirus (M4), which selectively blocks STAT3 signaling in tumor cells as a novel therapeutic strategy. M4 selectively replicated in tumor cells and expressed high levels of antisense STAT3 complementary DNA during the late phase of the viral infection in a replication-dependent manner. The viral progeny yield of M4 in tumor cells was much higher than that of the parent adenoviral mutants, Ad5/dE1A. M4 effectively silenced STAT3 and its target genes in tumor cells while sparing normal cells and exhibited potent antitumoral efficacy in vitro and in vivo. Systemic administration of M4 significantly inhibited tumor growth in an orthotopic gastric carcinoma mouse model, eliminated abdominal cavity metastases and prolonged survival time. In summary, M4 has low toxicity and great potential as a therapeutic agent for different types of cancers.
Carcinogenesis 10/2009; 30(12):2014-22. · 5.70 Impact Factor
-
Shuang Li,
Ping Liu,
Lin Xi, Xuefeng Jiang,
Mingfu Wu,
Dongrui Deng,
Juncheng Wei,
Tao Zhu,
Li Zhou,
Shixuan Wang,
Gang Xu,
Li Meng,
Jianfeng Zhou,
Ding Ma
[show abstract]
[hide abstract]
ABSTRACT: The high-risk human papillomavirus oncoprotein 18 E6 (HPV18 E6) is associated with cervix cancer. This study was conducted in order to identify the transmembrane protein 87B (TMEM87B) as a novel binding protein interacting with the HPV18 E6 oncoprotein and to perform an initial bioinformatics analysis. The yeast strain AH109 was transformed with pGBKT7-HPV18 E6 and the yeast mating assay was utilized to identify the interaction between TMEM87B and HPV18 E6 in the human Hela cDNA library. TMEM87B mRNA was detected in Hela cells by using RT-PCR. The TMEM87B gene structure, genomic localization, physical and chemical characteristics, subcellular localization and functional domain were predicted, as well as the systematic evolution analysis on similar proteins among several species. In the yeast two-hybrid assay, HPV18 E6 mRNA was expressed and there was no self-activation and toxicity in the AH109 strain. The special TMEM87B mRNA expression was detected in Hela cells and the blue clones were validated by the yeast mating assay. An efficient bioinformatics analysis fundamentally identified that TMEM87B is a secretary protein, containing many phosphorylation sites and functional motifs and possibly involved in signal transduction and transcriptional control in carcinogenesis. It was indicated that the yeast two-hybrid system is efficient for screening interacting proteins. The novel gene TMEM87B may interact with HPV18 E6 and may be a potential oncogenesis target according to the bioinformatics analysis.
Oncology Reports 08/2008; 20(2):421-7. · 1.84 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: To screen for novel binding proteins interacting with high-risk HPV 18 E6 oncogene, the strain AH109 was transformed with pGBKT7-HPV18 E6 plasmid, and subsequent transference was utilized to screen for interacting proteins with HPV 18 E6 in human Hela cDNA library. HPV18 E6 mRNA was expressed in yeast and there was no self-activation and toxicity in AH109. Seven proteins that interacted with HPV18 E6, including transmembrane protein 87B, phosphonoformate immuno-associated protein 5, vimentin, KM-HN-1 protein, dedicator of cytokinesis 7, vaccinia related kinase 2 and a hypothetical protein, were identified. It was suggested that yeast two-hybrid system is an efficient for screening interacting proteins. The high-risk HPV 18 E6 oncogene may interact with the proteins, which may be associated with signal transduction and transcriptional control, epithelial cell invasion and migration, as well as humoral and cellular immune etc. This investigation provides functional clues for further exploration of potential oncogenesis targets for cancer biotherapy.
Journal of Huazhong University of Science and Technology 03/2008; 28(1):93-6. · 0.38 Impact Factor
