Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C1140680 (ovarian cancer)
 28,141 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Clear cell carcinoma (CCC) of the ovary is known to be highly resistant to platinum-based chemotherapy. The purpose of our study was to identify a candidate protein that is associated with chemoresistance of CCC and to investigate the specific mechanism of chemoresistance conferred by the identified protein. Enhanced expression of Annexin A4 (Anx A4) was identified in ovarian CCC cells using 2-D differential gel electrophoresis (2D-DIGE) and mass spectrometry. Anx A4 levels were elevated in CCC cells compared with non-CCC cells as determined by real-time RT-PCR and Western blot analysis. Immunohistochemical analysis of Anx A4 was performed in 126 epithelial ovarian cancer tissue samples and demonstrated significantly elevated levels of Anx A4 protein levels in ovarian CCC tumors compared with ovarian serous and endometrioid tumors (p < 0.01). Anx A4-transfected ovarian non-CCC cells were more resistant to carboplatin (IC50 = 42 microM) compared with control cells (IC50 = 23 microM) as determined by modified MTT assay. Intracellular platinum levels were significantly lower in Anx A4-transfected cells compared with control cells after carboplatin treatment (p = 0.0020) and after an additional 360 min of carboplatin-free incubation (p = 0.0004), as measured by atomic absorption spectrophotometry. Expression of Anx A4 is elevated in ovarian CCC tumors and is associated with chemoresistance in cultured ovarian cancer cells. These results demonstrate that Anx A4 confers chemoresistance in ovarian cancer cells in part by enhancing drug efflux. Thus, Anx A4 may represent a novel therapeutic target of chemoresistance in patients with ovarian CCC.
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PMID:Enhanced expression of Annexin A4 in clear cell carcinoma of the ovary and its association with chemoresistance to carboplatin. 1959 62

Platinating agents constitute the first line treatment for ovarian cancer but treatment failure is common because of intrinsic and acquired resistance. Cancer cells develop the RASP-phenotype (cross resistance against arsenite, antimonite and platinum) associated with decreased accumulation of cisplatin and arsenite. ASNA1 is a possible subunit of a transport system for cisplatin and arsenite due to homology to arsA, an ATPase in the E. coli ars-complex responsible for efflux of arsenite and antimonite. Eukaryotic ASNA1 is a targeting factor for membrane insertion of tail-anchored proteins involved in the secretory pathway and cellular stress responses. The purpose with this study was to evaluate if ASNA1 expression influenced cisplatin, carboplatin, oxaliplatin or arsenite sensitivity in ovarian cancer. Human ovarian cancer cell line 2008 was transfected with a sense or an antisense ASNA1 construct. ASNA1 downregulated and overexpressing clones were identified by Western blots. Cell growth and chemosensitivity was determined by the MTT assay. Down-regulated ASNA1 expression was associated with retarded growth and increased sensitivity to cisplatin, carboplatin, oxaliplatin and arsenite whereas the cisplatin resistant 2008/A overexpresses ASNA1. These observations support the hypothesis that ASNA1 is a target to overcome platinum resistance in ovarian cancer.
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PMID:Increased sensitivity to platinating agents and arsenite in human ovarian cancer by downregulation of ASNA1. 1972 67

Newer series of 9-ethyl-9H-purine derivatives (EPD) were synthesized and screened for their efficacy in inhibiting the proliferation of various tumor cells in vitro. We evaluated the effects of EPD against HeLa, SiHa, CaSki (human cervical cancer cells), LM8, LM8G7 (murine osteosarcoma cells), OVSAHO and SKOV-3 (human ovarian cancer cells). The chemical structures of the EPD were confirmed by (1)H NMR and LCMS analyses. The inhibitory effects of EPD were studied by using trypan blue exclusion, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and TetraColor One reagents. Furthermore, SAR studies revealed that the presence of trifluoromethoxy and trifluromethyl group in 4b and 4g, respectively are responsible for the significant activity of the EPD against cervical cancer cells and the presence of isopropoxy group in 4f has influence in inhibiting the proliferation of osteosarcoma and ovarian cancer cell types.
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PMID:Synthesis, characterization and in vitro anti-tumor activities of novel 9-ethyl-9H-purine derivatives. 1975 77

Drug resistance is a major concern in the successful treatment of ovarian cancer. In the present study we report a combinational drug regime using arsenic trioxide (ATO) and cisplatin (CDDP) to increase therapeutic potentiality in ovarian cancer cells. ATO-mediated growth inhibition and apoptosis in human suspension ovarian cancer COC1 cells were evaluated by MTT assay and annexin V assay using flow cytometry, respectively. cDNA arrays were performed to screen ATO-mediated gene expression. Treatment of COC1 cells with ATO alone resulted in growth inhibition and apoptosis with a dose-and time-dependent fashion; further cDNA arrays showed that 34 genes (23 up-regulated genes and 11 down-regulated genes) may strongly associate with the antiproliferative and pro-apoptotic effects induced by ATO. Furthermore, Chou-Talalay analysis was used to evaluate the combinational effect of ATO and CDDP as well as dose-reduction index (DRI) in a panel of ovarian cancer cells including CDDP-sensitive and -resistant cell lines. The combination index (CI) analysis indicated that the interaction effect of ATO/CDDP exhibited a wide range of synergism in all the adherent ovarian cancer cells (A2780, IGROV-1, SKOV-3, and R182) as well as 0.93 to 0.69 for IC(50) to IC(90) in suspension COC1 cells where CI < 1, =1, and >1, define synergism, additive effect, and antagonism, respectively. More intriguingly, the combination of ATO and CDDP yielded favorable DRIs ranging from 1.23-fold to 13.51-fold dose reduction. These results suggest that ATO and its combination with CDDP present therapeutic potential for ovarian cancer, and deserve further preclinical and clinical studies.
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PMID:Arsenic trioxide and cisplatin synergism increase cytotoxicity in human ovarian cancer cells: therapeutic potential for ovarian cancer. 1976 30

Advanced ovarian cancer has a high rate of recurrence and mortality despite relative chemosensitivity at the time of initial treatment. Conventional chemotherapeutic agents typically target rapidly dividing cells. Disease relapse may therefore result from the survival and later emergence of latent slow-proliferating and/or quiescent cancer cells. We sought to identify drugs that target this cell population and to investigate the influence of these cells on outcome of patients in remission from advanced ovarian cancer. Drugs with increased efficacy against slower proliferating cells were identified using correlation-based screening of 44,657 compounds tested on the NCI-60 panel of cancer cell lines. Validation of candidates was performed in comparison with Cisplatin or Paclitaxel and by manipulation of proliferation rates by serum deprivation. Cytostatic and cytocidal effects were evaluated using MTT assays and active caspase-3 immunocytochemistry. Ki-67 proliferation indices were determined for tumors from 104 patients in remission. UCN-01 efficacy was correlated with longer doubling time among the NCI-60 cell lines (R = 0.54, p < 0.0001) and in a panel of 24 ovarian cancer cell lines (R = 0.42, p = 0.04), whereas this was not the case for Cisplatin (R = -0.10, p = 0.65) and Paclitaxel efficacy correlated with shorter doubling time (R = -0.52, p = 0.009). Cytostatic and cytocidal effects of UCN-01 were increased in serum-deprived cells. A low proliferation index was associated with presence of persistent disease at second-look surgery (p = 0.01) and poor survival (disease-free survival, p = 0.002; overall survival, p = 0.04). These results suggest that targeting quiescent ovarian cancer cells may be a worthwhile therapeutic approach to improving survival of women with ovarian cancer.
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PMID:Targeting slow-proliferating ovarian cancer cells. 1979 52

Ndc80 has been shown to play an important role in stable microtubule-kinetochore attachment, chromosome alignment, and spindle checkpoint activation in mitosis. It is composed of two heterodimers, CDCA1-KNTC2 and SPC24-SPC25. Overexpression of CDCA1 and KNTC2 is reported to be associated with poor prognosis in non-small cell lung cancers (NSCLC), and siRNA-mediated knockdown against CDCA1 or KNTC2 has been found to inhibit cell proliferation and induction of apoptosis in NSCLC, ovarian cancer, cervical cancer and glioma. Therefore, CDCA1 and KNTC2 can be considered good candidates for molecular target therapy as well as diagnosis in some cancers. However, the role of the Ndc80 complex in colorectal and gastric cancers (CRC and GC) still remains unclear. In the present study, we used qRT-PCR to evaluate the expression levels of CDCA1, KNTC2, SPC24 and SPC25 in CRC and GC and employed siRNA-mediated knockdown to examine cell proliferation and apoptosis. mRNA overexpression of these four genes was observed in CRCs and GCs when compared with the corresponding normal mucosae. Additionally, the expression levels of tumor/normal ratios of CDCA1, KNTC2, SPC24 and SPC25 correlated with each other in CRCs. MTT assays revealed that cell growths after the siRNA-mediated knockdown of either CDCA1 or KNTC2 were significantly suppressed, and flow cytometry analyses revealed significant increases of the subG1 fractions after knockdown against both genes. Our present results suggest that expressional control of component molecules of Ndc80 can be utilized for molecular target therapy of patients with CRC and GC.
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PMID:siRNA-mediated knockdown against CDCA1 and KNTC2, both frequently overexpressed in colorectal and gastric cancers, suppresses cell proliferation and induces apoptosis. 1987 54

In previous studies, rhein, one of the major bioactive constituents in the rhizome of rhubarb, inhibited the proliferation of various human cancer cells. However, because of its water insolubility, the anti-tumor efficacy of rhein was limited in vivo. In this study, we observed the anti-tumor activity of rhein lysinate (the salt of rhein and lysine easily dissolves in water) in vivo and investigated its mechanism. Inhibition of ovarian cancer SKOV-3 cell proliferation was determined by MTT assay and the mechanism of action of rhein lysinate was investigated by Western blot analysis. The therapeutic efficacy of rhein lysinate was evaluated by intragastric and intraperitoneal administrations in H22 hepatocellular carcinoma mice. Rhein lysinate inhibited the proliferation of SKOV-3 cells and the IC50 value was 80 microM. Rhein lysinate inhibited the phosphorylation of MEK and ERK and increased the anti-tumor activity of Taxol in vitro. It inhibited tumor growth by both intragastric and intraperitoneal administrations and improved the therapeutic effect of Taxol in H22 hepatocellular carcinoma mice. In conclusion, rhein lysinate offers an anti-tumor activity in vivo and is hopeful to be a chemotherapeutic drug.
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PMID:Rhein lysinate suppresses the growth of tumor cells and increases the anti-tumor activity of Taxol in mice. 1988 52

This study examined the effects of ursolic acid (UA) on the proliferation and apoptosis of a human ovarian cancer cell line, CAOV3. The CAOV3 cells were cultured in the RPMI 1640 media and treated with different concentrations of UA (0, 10, 20, 40 micromol/L). The proliferation rate of the CAOV3 cells was determined by MTT assay. The apoptosis rate was measured by flow cytometry. ERK activity was detected by immunoprecipitation and the expressions of p-ERK1/2, MKP-1, Bax and Bcl-2 by Western blotting. The results showed that the proliferation rate was significantly decreased in the cells treated with UA as compared with that in the non-treated cells (P<0.05). The intracellular ERK activity and p-ERK1/2 expression were also reduced in the UA-treated cells, while the MKP-1 expression was elevated. Moreover, the apoptosis was found in the CAOV3 cells exposed to UA; the Bax expression was increased and the Bcl-2 expression decreased. The apoptosis rate in the UA-treated cells was much higher than that in the non-treated cells (P<0.05). It is concluded that UA can inhibit the proliferation of CAOV3 cells by suppressing the ERK activity and the expression of p-ERK1/2. And it can also induce the apoptosis of the CAOV3 cells by up-regulating the Bax expression and down-regulating the Bcl-2 expression.
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PMID:Effects of ursolic acid on the proliferation and apoptosis of human ovarian cancer cells. 2003 23

OBJECTIVE.: Despite advances in chemotherapy and radical surgery, most advanced stage ovarian cancer patients die from their disease, highlighting the need for the development of novel treatment strategies. The Notch signaling pathway plays an important role in cellular differentiation, proliferation and apoptosis. We hypothesized that the active form of Notch 1, the Notch 1 intracellular domain (NICD), would be overexpressed in ovarian cancer cells and that depletion of NICD would lead to growth reduction. METHODS.: Following institutional review board approval, NICD expression was analyzed in human ovarian cancer specimens as well as the ovarian cancer cell lines OVCAR3, SKOV3, and CaOV3. In addition, the effects of Notch 1 depletion on ovarian cancer cell growth were detected by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) growth assay for 6 days following transfection with siRNA against Notch 1. RESULTS.: Western blot analysis revealed abundant NICD expression in all 3 ovarian cancer cell lines, as well as in 16 of 21 (76%) human ovarian cancer samples. Following treatment with Notch 1 siRNA, expression of NICD was greatly reduced in all three cell lines. Furthermore, this depletion of NICD was associated with significant growth inhibition of all three ovarian cancer cell lines. CONCLUSIONS.: NICD was frequently expressed in ovarian cancer cell lines and human ovarian cancer specimens. Importantly, depletion of Notch 1 led to growth inhibition of ovarian cancer cells. These findings support the hypothesis that Notch 1 plays a role in ovarian cancer proliferation, encouraging the investigation of this pathway as a therapeutic target.
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PMID:Notch 1 signaling is active in ovarian cancer. 2006 May 75

The release of Notch intracellular domain (NICD) is mediated by gamma-secretase. gamma-Secretase inhibitors have been shown to be potent inhibitors of NICD. We hypothesized that Notch1 is acting as an oncogene in ovarian cancer and that inhibition of Notch1 would lead to inhibition of cell growth and apoptotic cell death in ovarian cancer cells. In this study, expressions of Notch1 and hes1 in four human ovarian cancer (A2780, SKOV3, HO-8910, and HO-8910PM), and one ovarian surface (IOSE 144) cell lines were detected by Western blot and quantitative real-time RT-PCR. The effects of gamma-secretase inhibition (N-[N-(3,5-difluorophenacetyl)-l-alanyl]-S-phenylglycine t-butyl ester, DAPT) were measured by MTT assay, flow cytometry, ELISA and colony-forming assay. Our results showed that Notch1 and hes1 were found in all the four human ovarian cancer and IOSE 144 cell lines, and they were significantly higher in ovarian cancer cells A2780 compared to another four ovarian cells. Down-regulation of Notch1 expression by DAPT was able to substantially inhibit cell growth, induce G1 cell cycle arrest and induce cell apoptosis in A2780 in dose- and time-dependent manner. In addition, hes1 was found to be down-regulated in dose- and time-dependent manner by DAPT in A2780. These results demonstrate that treatment with DAPT leads to growth inhibition and apoptosis of A2780 cells in dose- and time-dependent manner. These findings also support the conclusion that blocking of the Notch1 activity by gamma-secretase inhibitors represents a potentially attractive strategy of targeted therapy for ovarian cancer.
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PMID:Down-regulation of Notch1 by gamma-secretase inhibition contributes to cell growth inhibition and apoptosis in ovarian cancer cells A2780. 2011 93


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