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)

S100P is a member of the S100 family of calcium-binding proteins. Our previous studies have demonstrated its significant downregulation in oxaliplatin-resistant colon cancer cell line. The present study investigated whether it plays a role in the regulation of chemosensitivity to anticancer drugs using human ovarian cancer cell line OVCAR3. We firstly overexpressed S100P in the OVCAR3 cell line, and evaluated the expression level of S100P by semiquantitative RT-PCR, Western blotting and immunofluorescence assay. 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium (MTT) assay indicated that overexpression of S100P sensitized OVCAR3 cells for chemotherapeutic drugs (paclitaxel, oxaliplatin, 5-fluorouracil, etoposide and epirubicin) induced cytotoxicity more than vector-only controls. Further studies showed that downregulation of S100P by RNA interference in OVCAR3 cells led to a significant increase of resistance to each of these anticancer drugs. Taken together, our results suggest that S100P plays an important role in regulation of chemosensitivity to anticancer drugs in ovarian cancer cells. Using S100P as a molecular biomarker may increase our ability to predict tumor drug response in ovarian cancer.
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PMID:S100P contributes to chemosensitivity of human ovarian cancer cell line OVCAR3. 1863 93

Published reports implicate a variety of mechanisms that may contribute to drug resistance in ovarian cancer. The chief aim of this study is to understand the relationship between overexpression of drug resistance associated genes and multidrug resistance in ovarian cancer. Using lentiviral short hairpin RNA collections targeting 132 genes identified from transcriptional profiling of drug-resistant cancer cell lines, individual knockdown experiments were done in the presence of sublethal doses of paclitaxel. Specific genes whose knockdown was found to be associated with cellular toxicity included MDR1 (ABCB1), survivin, and pre-mRNA processing factor-4 (PRP-4). These genes, when repressed, can reverse paclitaxel resistance in the multidrug-resistant cell line SKOV-3(TR) and OVCAR8(TR). Both MDR1 and survivin have been reported previously to play a role in multidrug resistance and chemotherapy-induced apoptosis; however, the effect of PRP-4 expression on drug sensitivity is currently unrecognized. PRP-4 belongs to the serine/threonine protein kinase family, plays a role in pre-mRNA splicing and cell mitosis, and interacts with CLK1. Northern analysis shows that PRP-4 is overexpressed in several paclitaxel-resistant cell lines and confirms that PRP-4 expression could be significantly repressed by PRP-4 lentiviral short hairpin RNA. Both clonogenic and MTT assays confirm that transcriptional repression of PRP-4 could reverse paclitaxel resistance 5-10-fold in SKOV-3(TR). Finally, overexpression of PRP-4 in drug-sensitive cells could induce a modest level of drug resistance to paclitaxel, doxorubicin, and vincristine.
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PMID:Lentiviral short hairpin RNA screen of genes associated with multidrug resistance identifies PRP-4 as a new regulator of chemoresistance in human ovarian cancer. 1868 98

The objective of this study was to evaluate the cytotoxicity and pharmacokinetics of total and lactone forms of 9-nitrocamptothecin (9-NC), an effective antineoplastic drug, after intravenous injection of drug incorporated into poly (DL-lactic-glycolic acid) nanoparticles (NPs). Drug-loaded NPs (9-NC.NP) were prepared by the nanoprecipitation method and examined for particle characteristics and in-vitro release in phosphate buffered saline. The best formulation showed a narrow size with an average diameter of 207+/-26 nm and a drug loading of more than 33.5%. The drug release profile showed a sustained 9-NC release up to 160 h. For a pharmacokinetic study, the concentration of 9-NC as the lactone form (9-NC.lac) and as the total of the lactone and carboxylate forms (9-NC.tot) in plasma was determined by using reverse-phase high performance liquid chromatography after intravenous administration of 9-NC.NP and a control solution to cannulated Wistar rats. In-vitro cytotoxic activity of 9-NC.NP and control solution was evaluated on the human ovarian cancer cell line (A2780sn) by MTT cell cytotoxicity assay. Results of in-vivo studies showed that NP encapsulation markedly increased the plasma concentration of both lactone and total forms of 9-NC compared with free drug. In comparison with free drug, NPs resulted in 3.63-fold and 5.40-fold increases in area under the plasma concentration-versus-time curve (AUC(0-infinity)) for lactone and total forms of 9-NC, respectively. The values of mean residence time and elimination half-life (T(1/2)) were also significantly higher for NPs than for free drug. The in-vitro cytotoxicity study revealed that the IC50 value of NPs decreased 10-fold compared with the drug solution. Prepared NPs described here were considered potentially useful in both stabilizing and delivering 9-NC and enhancing the efficacy of this drug for cancer treatment for which high drug retention in the body, protection from the drug-active lactone form, and gradual drug release appeared to be related.
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PMID:9-nitrocamptothecin polymeric nanoparticles: cytotoxicity and pharmacokinetic studies of lactone and total forms of drug in rats. 1869 92

Diverse types of voltage-gated potassium (K+) channels have been shown to be involved in regulation of cell proliferation. The maxi-conductance Ca2+-activated K+ channels (BK channels) may play an important role in the progression of human cancer. To explore the role of BK channels in regulation of apoptosis in human ovarian cancer cells, the effects of the specific BK channel activator NS1619 on induction of apoptosis in A2780 cells were observed. Following treatment with NS1619, cell proliferation was measured by MTT assay. Apoptosis of A2780 cells pretreated with NS1619 was detected by agarose gel electrophoresis of cellular DNA and flow cytometry. Our data demonstrate that NS1619 inhibits the proliferation of A2780 cells in a dosage and time dependent manner IC50=31.1 microM, for 48 h pretreatment and induces apoptosis. Western blot analyses showed that the anti-proliferation effect of NS1619 was associated with increased expression of p53, p21, and Bax. These results indicate that BK channels play an important role in regulating proliferation of human ovarian cancer cells and may induce apoptosis through induction of p21(Cip1) expression in a p53-dependent manner.
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PMID:The potassium ion channel opener NS1619 inhibits proliferation and induces apoptosis in A2780 ovarian cancer cells. 1870 95

The biological activities of sequential combinations of anticancer drugs, SOS thiophene (SOS) and mesochlorin e 6 monoethylenediamine (Mce 6), in the form of free drugs, nontargeted N-(2-hydroxypropyl)methacrylamide (HPMA) copolymer-drug conjugates, P-GFLG-Mce 6 and P-GFLG-SOS (P is the HPMA copolymer backbone and GFLG is the glycylphenylalanylleucylglycine spacer), and Fab'-targeted HPMA copolymer-drug conjugates, P-(GFLG-Mce 6)-Fab' and P-(GFLG-SOS)-Fab' (Fab' from OV-TL16 antibodies complementary to CD47), were evaluated against human ovarian carcinoma OVCAR-3 cells. Mce 6, SOS, P-GFLG-Mce 6, P-GFLG-SOS, P-(GFLG-Mce 6)-Fab', and P-(GFLG-SOS)-Fab', when used as single agents or in binary combination, exhibited cytotoxic activities against OVCAR-3 cells, as determined using a modified MTT assay. The binding and internalization of P-(GFLG-Mce 6)-Fab' and P-(GFLG-SOS)-Fab' by OVCAR-3 cells were visualized by confocal microscopy and flow cytometry. The results confirmed an enhanced biorecognition by OVCAR-3 cells of Fab'-targeted HPMA copolymer conjugates over nontargeted conjugates. The median-effect analysis and the determination of the combination index (CI) were used to describe the drug interaction and quantify the synergism, antagonism, or additivity in anticancer effects. The sequential combinations of SOS+Mce 6 and P-GFLG-SOS+P-GFLG-Mce 6 displayed very strong synergism to synergism in the entire range of cell inhibition levels ( f a = 0.5 - 0.95). The P-(GFLG-SOS)-Fab'+P-(GFLG-Mce 6)-Fab' exhibited a strong synergism for f a values up to about 0.85, but showed synergistic effect and nearly additive effect at f a = 0.9 and 0.95, respectively. These observations support the continuation of in vivo investigations of these conjugates for the treatment of ovarian cancer.
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PMID:Combination chemotherapy and photodynamic therapy with fab' fragment targeted HPMA copolymer conjugates in human ovarian carcinoma cells. 1872 68

We assessed changes in the apoptosis-related genes BCL2, BAX, BCL2L12, FAS and CASPASE-3 in OVCAR-3 human ovarian cancer cells and BT-20 human breast cancer cells to provide an insight into the molecular mechanisms involved in the response of these cells to treatment with anticancer drugs and to assess their value as potential biomarkers of chemotherapy response in breast and ovarian cancer. Cells were treated with different chemotherapeutic drugs (cisplatin, carboplatin, doxorubicin, etoposide and taxol) and assessed for changes in the expression of apoptosis-related genes at the mRNA level. Total RNA was extracted, reverse-transcribed into cDNA and amplified by PCR using gene-specific primers. GAPDH was used as a housekeeping gene. Cytotoxicity was assessed by MTT assay. Both cancer cell lines responded differentially at the molecular level to the drug treatments. OVCAR-3 cells showed more pronounced sensitivity and changes compared to BT-20 cells at the mRNA level for different apoptosis-related genes, leading to cell and cancer type dependence in conjunction with drug dependence.
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PMID:Molecular profile of breast versus ovarian cancer cells in response to treatment with the anticancer drugs cisplatin, carboplatin, doxorubicin, etoposide and taxol. 1878 38

Hypoxia inducible factor 1alpha (HIF-1alpha) regulates the transcription of a number of genes under hypoxia and other extracellular or intracellular stimulations. It also promotes angiogenesis, tumor metastasis and invasion. To investigate the effect of hypoxia and reoxygenation on cell proliferation, invasion and adhesion, which are all related to ovarian cancer, we applied chemically-induced hypoxia in the cultured human ovarian carcinoma cell line, HO-8910PM. Semi-quantitative RT-PCR results show that CoCl2 induces the expression of HIF-1alpha in a time- and dose-dependent manner. MTT assay results show that CoCl2-induced hypoxia inhibits cell proliferation which is recovered by reoxygenation. The Boyden and cell adhesion test results indicate that CoCl2-induced hypoxia inhibits cell invasion and adhesion which are markedly enhanced by reoxygenation in the human ovarian carcinoma cell line, HO-8910PM. Collectively, our data provide insight into understanding molecular mechanisms of the invasiveness of ovarian cancer under the conditions of hypoxia and reoxygenation.
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PMID:Effect of hypoxia and re-oxygenation on cell invasion and adhesion in human ovarian carcinoma cells. 1881 21

Adenovirus (ADV)-mediated gene therapy with the thymidine kinase (TK) gene under control of the Rous sarcoma virus (RSV) promotor followed by the administration of acyclovir has been established in vitro for the treatment of ovarian cancer cells and has been used as the basis for intraperitoneal phase I clinical trials. It is unclear how long a significant degree of transgene translation can be expected after adenovirus-mediated TK transduction, where the transcriptional complex is localized in the nucleus in an episomal fashion and thus without stable integration. The possible interaction of acyclovir pretreatment with subsequent ADV-RSV-TK transduction also remains to be elucidated. Transgene expression and cell killing efficacy were analysed based on multiplicity of infection (MOI) and MTT assay. Anti-TK-antibody 1397 was used for immunocytochemistry and Western blot analysis of TK expression. After transduction with ADV-RSV-TK at an MOI of 66, TK translation increased strongly in MDH 2774 and OVCAR-3 cell lines during the initial 48 hours. Virtually constant expression of the TK transgene was observed by Western blot during eight days. Cell killing efficacy was increased by repeated daily administrations of acyclovir. Pretreatment with acyclovir did not result in significantly increased cell killing efficacy. No negative effect of acyclovir on ADV-RSV-TK transduction was observed. The at least week-long expression of the TK transgene with persistently increasing efficacy of cell killing after ADV-mediated tumor cell transduction provide a realistic basis for the development of multicycle ADV-mediated TK gene therapy approaches in the treatment of ovarian cancer. Continuous i.v. acyclovir treatment or daily oral acyclovir-prodrug therapy might simplify the substrate regimen for the TK gene.
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PMID:Persistent adenovirus-mediated thymidine kinase gene expression in ovarian cancer cells increases cell killing efficacy over time. 1903 80

The camptothecins, which target the intranuclear enzyme topoisomerase I, have advanced to the forefront of several areas of developmental chemotherapy of cancers. In the present study, we investigated the potential anti-human ovarian cancer effects of NSC606985, a novel and rarely studied camptothecin analog, and its combination with cisplatin (CDDP). Human ovarian cancer cell line COC1 cells were treated with different nanomolar of NSC606985 with or without CDDP, and cell growth and apoptosis were evaluated, respectively, by MTT assay and annexin-V assay on flow cytometry. Chou-Talalay analysis was used to evaluate combined effect of NSC606985 and CDDP. Western blot was used to detect protein kinase Cdelta (PKCdelta), caspase-3 and hypoxia-inducible factor-1alpha (HIF-1alpha) proteins. Our results showed that NSC606985 at nanomolar concentration induced apoptosis with the activation of PKCdelta in COC1 cells. Especially, NSC606985 presented the significant combined effects on COC1 cells in terms of growth inhibition and apoptosis induction. In addition, NSC606985 significantly antagonized the accumulation of HIF-1alpha stabilized by hypoxia or hypoxia-mimetic agent. These results suggest that NSC606985 and its combination with CDDP present the therapeutic potential on ovarian cancer, and deserve further preclinical and clinical studies.
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PMID:NSC606985 induces apoptosis, exerts synergistic effects with cisplatin, and inhibits hypoxia-stabilized HIF-1alpha protein in human ovarian cancer cells. 1933 7

Ovarian cancer has the highest mortality rate among gynecologic malignancies in the world, and the development of drug resistance is a major impediment toward successful treatment of the desease. Emodin has been reported to sensitize human tumor cells to chemotherapeutic agents. The present study investigated whether emodin could overcome chemoresistance of A2780/taxol cells. Cells were treated with different concentration of emodin alone or combined with paclitaxel, then the cell viability was measured by MTT and the apoptosis was determined by flow cytometric analysis. The changes of mRNA and protein were examined by QRT-PCR and Western blotting. The function of P-glycoprotein was also determined by flow cytometry. The results showed that emodin induced apoptosis alone at a high concentration and increased paclitaxel-induced apoptosis at a low concentration. It enhanced the sensitivity of A2780/taxol cells to paclitaxel with down-regulation of P-glycoprotein, XIAP and survivin. Taken together, the results demonstrated a dual role for emodin in the inhibition of drug resistant ovarian tumor growth by increasing paclitaxel cellular concentration and re-sensitizing the resistant cells to paclitaxel. Our results suggest the possibility of an innovative chemotherapeutic strategy that uses emodin in combination with paclitaxel to increase the sensitivity of tumor cells.
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PMID:Emodin sensitizes paclitaxel-resistant human ovarian cancer cells to paclitaxel-induced apoptosis in vitro. 1942 43


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