Ovarian Carcinoma Cell Lines Research Articles

Selenium-enriched polysaccharides from pyracantha fortuneana (Se-PFPs) augment docetaxel-induced tumor suppression in human ovarian cancer

Pyracantha fortuneana (Maxim.) contains many healthy ingredients, including selenium-enriched polysaccharides. Selenium-enriched polysaccharides from P. fortuneana (Se-PFPs) have anti-mutation and anti-oxidation activities, along with anti-tumor activity in ovarian cancer and breast cancer cells. Docetaxel (DTX) is widely applied in therapeutic treatment for ovarian cancer. However, its use in clinics is restricted due to its unfavorable side-effects. Thus there is a need to improve the therapeutic efficacy of Docetaxel (DTX). This study aimed to determine whether Se-PFPs and DTX can be used together to generate additive and/or synergistic effect in therapeutic treatment for ovarian cancer. In vitro and in vivo experiments were conducted to compare the anti-proliferative and apoptosis-inducing effects of the combined use of both drugs with that of each one used alone. Two ovarian carcinoma cell lines, SKOV3 and A2780 cells, were used and divided into four groups: 1) Saline control (vehicle); 2) Se-PFPs only; 3) DTX only; and 4) Se-PFPs+DTX. The apoptotic rate of group treated with a combination of Se-PFPs and DTX was found to be significantly higher than those of groups treated with either agent alone. This finding was confirmed by increased TdT-mediated dUTP nick end labeling (TUNEL)-positive rate, rate of apoptotic cells, enhanced cleavage of caspase-3 and PARP, and reduced cell viability and Ki-67 expression. The combined drugs did not significantly increase the toxicity HOSE cells, the human ovarian surface epithelial cells immortalized with hTERT. Similar results were obtained in the in vivo experiments by measuring tumor weight and volume. Thus, Se-PFPs can augment DTX tumor inhibitory effect. The combination of Se-PFPs and DTX can be a promising therapeutic strategy for ovarian cancer. Key words: Selenium-enriched Pyracantha fortuneana (Maxim.) Li polysaccharides, docetaxel, tumor suppression, ovarian cancer.

Studies on combination of oxaliplatin and dendrosomal nanocurcumin on proliferation, apoptosis induction, and long non-coding RNA expression in ovarian cancer cells.

Drug resistance remains a major challenge in the treatment of patients with ovarian cancer. Therefore, the development of new anticancer drugs is a clinical priority to develop more effective therapies. New approaches to improve clinical outcomes and limit the toxicity of anticancer drugs focus on chemoprevention. The aim of this study was to determine the effects of dendrosomal nanocurcumin (DNC) and oxaliplatin (Oxa) and their combination on cell death and apoptosis induction in human ovarian carcinoma cell lines analyzed by MTT assay and flow cytometry, respectively. The synergism effect of Oxa and DNC was analyzed using the equation derived from Chou and Talalay. In addition, real-time PCR was used to measure the effect of this combination on the expression levels of long non-coding RNAs with different expression in ovarian cancer and normal ovaries. Our data showed that the effect of DNC on cell death is more than curcumin alone in the same concentration. The greatest cell death effect was observed in combination of Oxa with DNC, while Oxa was added first, followed by DNC at 4h interval (0/4h). The findings indicated that DNC induced apoptosis significantly in both cell lines as compared to control groups; however, combination of both agents had no significant effect in apoptosis induction. In addition, combination of both agents significantly affects the relative expression of long non-coding RNAs investigated in the study as compared with mono therapy.

Induction of apoptosis in ovarian cancer cells by miR-493-3p directly targeting AKT2, STK38L, HMGA2, ETS1 and E2F5.

Apoptosis is a form of directed programmed cell death with a tightly regulated signalling cascade for the destruction of single cells. MicroRNAs (miRNAs) play an important role as fine tuners in the regulation of apoptotic processes. MiR-493-3p mimic transfection leads to the induction of apoptosis causing the breakdown of mitochondrial membrane potential and the activation of Caspases resulting in the fragmentation of DNA in several ovarian carcinoma cell lines. Ovarian cancer shows with its pronounced heterogeneity a very high death-to-incidence ratio. A target gene analysis for miR-493-3p was performed for the investigation of underlying molecular mechanisms involved in apoptosis signalling pathways. Elevated miR-493-3p levels downregulated the mRNA and protein expression levels of Serine/Threonine Kinase 38 Like (STK38L), High Mobility Group AT-Hook 2 (HMGA2) and AKT Serine/Threonine Kinase 2 (AKT2) by direct binding as demonstrated by luciferase reporter assays. Notably, the protein expression of RAF1 Proto-Oncogene, Serine/Threonine Kinase (RAF1) was almost completely downregulated by miR-493-3p. This interaction, however, was indirect and regulated by STK38L phosphorylation. In addition, RAF1 transcription was diminished as a result of reduced transcription of ETS proto-oncogene 1 (ETS1), another direct target of miR-493-3p. Taken together, our observations have uncovered the apoptosis inducing potential of miR-493-3p through its regulation of multiple target genes participating in the extrinsic and intrinsic apoptosis pathway.

The effects of crocetin, extracted from saffron, in chemotherapy against the incidence of multiple drug resistance phenotype.

Objective(s):Crocetin, one of the main substances of saffron extract, has anti-cancer effects. Drug resistance proteins (e.g. MRP1 and MRP2) are important reasons for the failure of cancer therapy. We intended to investigate the efficacy of crocetin on MRP1 and MRP2 activity in human ovarian cisplatin-resistant carcinoma cell line (A2780-RCIS).Materials and Methods: The cytotoxic effect of crocetin was evaluated by the MTT assay. The efficacy of crocetin on MRP1 and MRP2 expression at mRNA level was studied by real-time RT-PCR. The effect of crocetin on the activity of MRP transporters was determined by drug efflux assay.Results:Crocetin decreased cell proliferation in the A2780 (IC50: 183±7 µM) and A2780-RCIS (IC50: 316±9 µM). Crocetin decreased the expression level of MRP1 (22±2 %) and MRP2 (48±8 %) in A2780-RCIS and inhibited MRP pumps function directly in A2780 (44±1 %) and A2780-RCIS (88±10 %) and indirectly in A2780 (32±2 %) and A2780-RCIS (48±15 %) respectively. Conclusion:Our findings showed that crocetin could quench drug resistance through modulation of MRP transporters in the drug resistant human ovarian cancer cells.

Differential expression of mTOR components in endometriosis and ovarian cancer: Effects of rapalogues and dual kinase inhibitors on mTORC1 and mTORC2 stoichiometry

Endometriosis is a well-known risk factor for ovarian cancer. The genetic changes that characterise endometriosis are poorly understood; however, the mechanistic target of rapamycin (mTOR) pathway is involved. In this study, we investigated the expression of key mTOR components in endometriosis and the effects of rapalogues using an endometrioid ovarian carcinoma cell line (MDAH 2774) as an in vitro model. Gene expression of mTOR, DEPTOR, Rictor and Raptor was assessed by qPCR in 24 endometriosis patients and in silico in ovarian cancer patients. Furthermore, the effects of Rapamycin, Everolimus, Deforolimus, Temsirolimus, Resveratrol, and BEZ235 (Dactolisib, a dual kinase inhibitor) on mTOR signalling components was assessed. mTOR showed a significant increase in the expression in endometriosis and ovarian endometrioid adenocarcinoma patients compared to non-affected controls. DEPTOR, an inhibitor of mTOR, was downregulated in the advanced stages of ovarian cancer (III and IV) compared to earlier stages (I and II). Treatment of MDAH-2774 cells with the mTOR inhibitors resulted in the significant upregulation of DEPTOR mRNA, whereas treatment with rapamycin and BEZ-235 (100 nM) resulted in downregulation of the mTOR protein expression after 48 h of treatment. None of the treatments resulted in translocation of mTOR from cytoplasm to nucleus. Upregulation of DEPTOR is a positive prognostic marker in ovarian cancer and is increased in response to mTOR pathway inhibition suggesting that it functions as a tumour suppressor gene in endometrioid ovarian carcinoma. Collectively, our data suggest the mTOR pathway as a potential connection between endometriosis and ovarian cancer and may be a potential target in the treatment of both conditions.

Volatile Profiling, Insecticidal, Antibacterial and Antiproliferative Properties of the Essential Oils of Bursera glabrifolia Leaves.

The present article describes the chemical composition and biological activities of the essential oils of B. glabrifolia leaves obtained in four consecutive years (2015-2018). The essential oils contained α-terpineol (17.9-29.7 %), α-terpinene (12.6-17.4 %), limonene (14.9-26.8 %) and β-pinene (2.1-16.7 %) as the most abundant volatiles. The essential oils and these volatiles showed a significant adulticide activity (p<0.01; LC50 <100 μg mL-1 ) on the maize weevil (Sitophilus zeamais) with a 100 % mortality rate within a period of 5 h. Also, the essential oils showed a strong antibacterial activity on Enterococcus faecalis ATCC 29212 (MIC, 132.7-173.6 μg mL-1 ) and Helicobacter pylori ATCC 43504 (MIC, 74.8-199.2 μg mL-1 ). The assessment of the main volatiles revealed α-terpineol as the principal antibacterial agent (MIC, 78.6-149.7 μg mL-1 ). Similarly, the essential oils exhibited a substantial in vitro antiproliferative activity on the human prostate cancer cell lines PC-3 (LC50 , 15.2-19.4 μg mL-1 ), the human ovarian carcinoma cell lines OVCAR-3 (LC50 , 27.3-53.7 μg mL-1 ) and the myelogenous leukemia cell lines K-562 (LC50 , 32.4-75.9 μg mL-1 ). α-Terpineol (LC50 , 32.4-75.9 μg mL-1 ) exhibited the strongest antiproliferative effect on these cancer cell lines (LC50 , 22.4-48.1 μg mL-1 ).

Whole Cell MALDI Fingerprinting Is a Robust Tool for Differential Profiling of Two-Component Mammalian Cell Mixtures.

MALDI fingerprinting was first described two decades ago as a technique to identify microbial cell lines. Microbial fingerprinting has since evolved into an automated platform for microorganism identification and classification, which is now routinely used in clinical and environmental sectors. The extension of fingerprinting to mammalian cells has yet to progress partly due to compartmentalization of eukaryotic cells and overall higher cellular complexity. A number of publications on mammalian whole cell fingerprinting suggest that the method could be useful for classification of different cell types, cell states, and monitoring cell differentiation. We report the optimization of MALDI fingerprinting workflow parameters for mammalian cells and its application for differential profiling of mammalian cell lines and two-component cell line mixtures. Murine fallopian tube cells and high-grade ovarian carcinoma cell lines and their mixtures are used as model mammalian cell lines. Two-component cell mixtures serve to determine the method's feasibility for complex biological samples as the ability to detect cancer cells in a mixed cell population. The level of detection of cancer cells in the two-component mixture by principle component analysis (PCA) starts to deteriorate at 5% but with application of a different statistical approach, Wilcoxon rank sum test, the level of detection was determined to be 1%. The ability to differentiate heterogeneous cell mixtures will help further extend whole cell MALDI fingerprinting to complex biological systems. Graphical Abstract.

Inhibition of store-operated channels by carboxyamidotriazole sensitizes ovarian carcinoma cells to anti-BclxL strategies through Mcl-1 down-regulation.

The anti-apoptotic proteins Bcl-xL and Mcl-1 have been identified to play a pivotal role in apoptosis resistance in ovarian cancer and constitute key targets for innovative therapeutic strategies. Although BH3-mimetics (i.e. ABT-737) potently inhibit Bcl-xL activity, targeting Mcl-1 remains a hurdle to the success of these strategies. Calcium signaling is profoundly remodeled during carcinogenesis and was reported to activate the signaling pathway controlling Mcl-1 expression. In this context, we investigated the effect of carboxyamidotriazole (CAI), a calcium channel inhibitor used in clinical trials, on Mcl-1 expression. CAI had an anti-proliferative effect on ovarian carcinoma cell lines and strongly down-regulated Mcl-1 expression. It inhibited store-operated calcium entry (SOCE) and Mcl-1 translation through mTORC1 deactivation. Moreover, it sensitized ovarian carcinoma cells to anti-Bcl-xL strategies as their combination elicited massive apoptosis. Its effect on mTORC1 and Mcl-1 was mimicked by the potent SOCE inhibitor, YM58483, which also triggered apoptosis when combined with ABT-737. As a whole, this study suggests that CAI sensitizes to anti-Bcl-xL strategies via its action on Mcl-1 translation and that modulation of SOCE could extend the therapeutic arsenal for treatment of ovarian carcinoma.

HE4 suppresses the expression of osteopontin in mononuclear cells and compromises their cytotoxicity against ovarian cancer cells.

Ovarian cancers are known to evade immunosurveillance and to orchestrate a suppressive immune microenvironment. Here we examine the role of human epididymis protein 4 (HE4), an ovarian cancer biomarker, in immune evasion. Through modified subtractive hybridization analyses we have characterized the gene targets of HE4 in human peripheral blood mononuclear cells (PBMCs), and established a preliminary mechanism for HE4-mediated immune failure in ovarian tumours. Upon exposure of purified PMBCs to HE4, osteopontin (OPN) and dual-specificity phosphatase 6 (DUSP6) emerged as the most suppressed and up-regulated genes, respectively. SKOV3 and OVCAR8, human ovarian carcinoma cell lines, exhibited enhanced proliferation in conditioned media from HE4-exposed PBMCs, an effect that was attenuated by the addition of recombinant OPN or OPN-inducible cytokines [interleukin (IL)-12 and interferon (IFN)-Ɣ]. Additionally, upon co-culture with PBMCs, HE4-silenced SKOV3 cells were found to be more susceptible to cytotoxic cell death. The relationship between HE4 and OPN was reinforced further through the analysis of serous ovarian cancer patient samples. In these biopsy specimens, the number of OPN+ T cells correlated positively with progression free survival (PFS) and inversely with serum HE4 level. Taken together, these findings show that HE4 enhances ovarian cancer tumorigenesis by compromising OPN-mediated T cell activation.

LINK-A lncRNA promotes migration and invasion of ovarian carcinoma cells by activating TGF-β pathway.

Introduction: LINK-A lncRNA is a well-characterized oncogenic lncRNA only in triple negative breast cancer. Our study was carried out to investigate the possible involvement of LINK-A lncRNA in ovarian carcinoma. Methods: Expression of LINK-A in ovarian biopsies and plasma of both ovarian carcinoma patients and healthy females was detected by qRT-PCR. Plasma TGF-β1 was detected by ELISA. Correlation between plasma LINK-A and TGF-β1 was analyzed by Pearson correlation analysis. Correlation between plasma LINK-A and patients’ clinicopathological data was analyzed by Chi-square test. LINK-A overexpression vector was transfected into cells of human ovarian carcinoma cell lines. Cell migration and invasion were detected by Transwell migration and invasion assay. TGF-β1 expression was detected by Western blot. Results: We found that LINK-A and TGF-β1 were up-regulated in ovarian carcinoma patients than in healthy controls. Plasma levels of LINK-A were positively correlated with plasma TGF-β1 in ovarian carcinoma patients but not in healthy controls. Plasma levels of LINK-A were correlated with distant tumor metastasis but not tumor size. LINK-A overexpression led to up-regulated TGF-β1 in ovarian carcinoma cells and promoted cell migration and invasion. In contrast, TGF-β1 treatment showed no effects on LINK-A expression but attenuated the effects of LINK-A overexpression on cell migration and invasion. Conclusions: We conclude that LINK-A lncRNA may promote migration and invasion of ovarian carcinoma cells by activating TGF-β pathway.

Synthesis, characterisation and cytotoxicity studies of ruthenium arene complexes bearing trichlorogermyl ligands

The synthesis of five half sandwich ruthenium(II) trichlorogermyl complexes of the type [(η6-Arene)Ru(PR3)Cl(GeCl3)] (PR3 = Phosphane and phosphite ligands; Arene = p-cymene or C6H5-OC2H4OH) is reported: [(η6-p-cymene)Ru(P(OMe)3)Cl(GeCl3)] (1), [(η6-p-cymene)Ru(P(OPh)3)Cl(GeCl3)] (2), [(η6-p-cymene)Ru(PPh3)Cl(GeCl3)] (3), [(η6-p-cymene)Ru(pta)Cl(GeCl3)] (pta = 1,3,5-triaza-7-phosphaadamantane) (4) and [(η6-C6H5-OC2H4OH)Ru(pta)Cl(GeCl3)] (5). The nature of the η6-arene and phosphane ligand was varied and the complexes have been prepared by facile insertion of GeCl2 (from GeCl2.(dioxane)) into the Ru-Cl bonds of the respective easily accessible precursor complexes [(η6-Arene)Ru(PR3)Cl2]. The complexes were fully spectroscopically characterized by 1H, 13C{1H} and 31P{1H} NMR spectroscopy, UV-Vis, ATR-IR, HRMS (ESI) and their thermal behavior elucidated by TGA. Their cytotoxicity to human ovarian carcinoma (A2780) and non-tumorigenic human embryonic kidney HEK293 cell lines is also reported, and represents the first cytotoxic investigations of Ru(II) germyl complexes to date. The first DFT studies (B3LYP; basis set 6-31+G(d,p) for H, C, O, P, Cl, N, and Ge atoms and DGDZVP for Ru atom) on trichlorogermyl ruthenium complexes were carried out on complex 2 and 5 in order to gain insights into the bonding situation between Ru and Ge and are reported.

Retraction: Potentiation of Paclitaxel Activity by the HSP90 Inhibitor 17-allylamino-17-demethoxygeldanamycin in Human Ovarian Carcinoma Cell Lines with High Levels of Activated AKT.

This article (1) is being retracted at the request of the authors. The work is in two main parts. The first part is a description of the relevant characteristics of the human ovarian cancer cell lines used and an analysis of the efficacy of the combination of the HSP90 inhibitor 17-AAG with paclitaxel and carboplatin. The latter part shows the effect of the single agents and drug combinations on HSP90 client proteins and downstream effectors. All of the experiments in the article were carried out in the laboratory of the senior author A.L. Jackman. It has been brought to our attention that in the second part of the article, Figs. 5A, 5B, 6, 7, and 8 contained inappropriately assembled Western blots. N. Sain performed the experiments and processed the data and has taken primary responsibility for the flawed figures. The authors wish to sincerely apologize to the scientific community and deeply regret any inconveniences or challenges resulting from the publication and subsequent retraction of this article.

Antrodia salmonea-induced oxidative stress abrogates HER-2 signaling cascade and enhanced apoptosis in ovarian carcinoma cells.

Antrodia salmoneais well known in Taiwan as a traditional Chinese medicinal fungus and has demonstrated antioxidant, anti-inflammatory, and anticancer effects. However, the anticancer activity of A. salmonea against human ovarian cancer is still elusive. Therefore, we investigated the antiovarian tumor activity of a fermented culture broth of A. salmonea and exhibits its underlying molecular mechanism. A. salmonea shows a significant effect on cell viability in human ovarian carcinoma (SKOV-3 or A2780) cell lines with an 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. Increased terminal deoxynucleotidyl transferase dUTP nick-end labeling-positive cells and annexin V-propidium iodide stained cells indicate that A. salmonea induces late apoptosis in SKOV-3 cells. Notably, treatment with A. salmonea induced the following events: Apoptosis; caspase-3, -8, -9 and poly(ADP-ribose) polymerase activation; first apoptosis signal (Fas) and Fas ligand activation; Bid cleavage; and Bax2-B-cell lymphoma 2 dysregulation. The results show that A. salmonea-induced apoptosis was mediated by both mitochondrial and death receptor pathways. An increase in intracellular reactive oxygen species (ROS) was also observed in A. salmonea-treated cells, whereas the antioxidant N-acetylcysteine (NAC) prevented A. salmonea-induced cell death and DNA fragmentation, indicating that A. salmonea-induced apoptosis was mediated by ROS generation. Interestingly,A. salmonea-induced apoptosis is associated with the suppression of human epidermal growth factor receptor-2 (HER-2/neu) and phosphoinositide 3-kinase (PI3K)-protein kinase B (AKT) expression in HER-2/neu overexpressing SKOV-3 cells. NAC significantly prevented A. salmonea-induced HER-2/neu depletion and PI3K/AKT inactivation, indicating that A. salmonea-triggered apoptosis is mediated by ROS-inhibited HER-2/neu signaling cascades. To our knowledge, this is the first report describing the anticancer activity of this potentially beneficial mushroom against human ovarian carcinoma.

Characterization and drug sensitivity of a novel human ovarian clear cell carcinoma cell line genomically and phenotypically similar to the original tumor.

NUCOLL43 is a novel ovarian clear cell carcinoma (O‐CCC) cell line that arose from a primary culture of a patient's malignant ascites. The cells grow reliably in cell culture with a doubling time of approx. 45 hours and form colonies at high efficiency. They have a very high degree of loss of heterozygosity (LOH) affecting approximately 85% of the genome, mostly copy neutral and almost identical to the original tumor. The cells express epithelial (pan‐cytokeratin) and mesenchymal (vimentin) characteristics, CA125 and p16, like the original tumor. They also express ARID1A but not HNF‐1β and, like the original tumor, and are negative for p53 expression, with no evidence of p53 function. NUCOLL43 cells express all other DNA damage response proteins investigated and have functional homologous recombination DNA repair. They are insensitive to cisplatin, the PARP inhibitor rucaparib, and MDM2 inhibitors but are sensitive to camptothecin, paclitaxel, and NVP‐BEZ235. The NUCOLL43 cell line represents a distinct subtype of O‐CCC that is p53 and HNF‐1β null but expresses ARID1A. Its high degree of similarity with the original tumor genomically and proteomically, as well as the high level of LOH, make this an interesting cell line for O‐CCC research. It has been deposited with Ximbio.

Half-Sandwich Ir(III) Complex of N1-Pyridyl-7-azaindole Exceeds Cytotoxicity of Cisplatin at Various Human Cancer Cells and 3D Multicellular Tumor Spheroids

The half-sandwich iridium(III) complexes [Ir(η5-Cpx)(phaza–)Cl] (1, 2), [Ir(η5-Cpx)(thaza–)Cl] (3, 4), and [Ir(η5-Cpx)(pyaza)Cl]PF6 (5, 6) containing deprotonated 1-phenyl-7-azaindole (phaza–) and 1-(thiophen-2-yl)-7-azaindole (thaza–) and electroneutral 1-(pyridin-2-yl)-7-azaindole (pyaza), were prepared; Cpx = pentamethylcyclopentadienyl (Cp*; for 1, 3, and 5) or 1,2,3,4-tetramethyl-5-phenylcyclopentadienyl (Cpph; for 2, 4, and 6). The complexes were thoroughly characterized, including a single-crystal X-ray analysis of complexes 1, 5, and 6. All of the complexes were screened for their in vitro cytotoxicity at the A2780 human ovarian carcinoma cell line and its A2780R cisplatin-resistant variant (2D culture cells). The best-performing complex 6 was further studied against the human DU-145 prostatic carcinoma, A549 lung carcinoma, HCT116 colon carcinoma, HeLa cervix adenocarcinoma, and MCF7 breast adenocarcinoma cell lines (2D culture cells). Complex 6 showed a cytotoxic profile different from that of c...

Experimental and theoretical exploration of molecular structure and anticancer properties of two N, N′–disubstituted thiocarbamide derivatives

Two new compounds N-(2-chloro-4-nitrophenyl)-N'-(phenoxycarbonyl) thiocarbamide (1) and N-(2-chloro-4-nitrophenyl)-N'-(4-nitrobenzoyl) thiocarbamide (2), have been derived by the reaction of phenoxycarbonyl isothiocyanate/4-nitrobenzoyl isothiocyanate with 2-chloro-4-nitroaniline. The structures of these compounds were determined by spectroscopic (FT-IR, 1H and 13C NMR, UV–Visible) and single crystal X-ray studies. Both the crystal structures are symmetrical and planar with anti-periplanar orientation of CO and CS group. The molecular structure and vibrational properties of the compounds studied at B3LYP/6-311G ++ (d, p) level of density functional theory further concrete the experimental results. These compounds were screened for their in vitro cytotoxicity activity against seven human cancer cell lines; cervical (2008 and C13*), colorectal (HT29 and HCT116) and ovarian carcinoma (A2780, A2780/CP and IGROV-1). Compound 2 exhibited significant activity against all the cell lines whereas compound 1 demonstrated appreciable activity only against ovarian carcinoma cell lines.

PTP1B promotes the malignancy of ovarian cancer cells in a JNK-dependent mechanism

Ovarian cancer is the leading cause of death from gynecological malignancies in women. Diagnosis at the early stage remains challenging and efficient treatment is still highly needed. The development and progression of this cancer is associated with many genetic and epigenetic changes, representing the dysregulation of a highly complex signaling network. Previous studies found that protein-tyrosine phosphatase 1 B (PTP1B) was aberrantly expressed in many types of ovarian cancer cells. The exact role of this protein, however, remains controversial. We found that PTP1B was highly expressed in several ovarian carcinoma cell lines. Changing its expression level strongly affected the malignancy phenotypes of the cultured cancer cells and growth of tumors in nude mice. Further analysis at the molecular level found that overexpression of PTP1B activated the JNK (c-Jun N-terminal kinase) signaling pathway and impacted a set of factors involved in cancer metastasis. Overall, our study suggested that overexpression of PTP1B could be a driving factor in the tumorigenesis and progression of ovarian cancer and restoring the normal expression level of this signaling molecule may represent a promising strategy in treating this disease.

Half-sandwich Ir(III) and Rh(III) 2,2′-dipyridylamine complexes: Synthesis, characterization and in vitro cytotoxicity against the ovarian carcinoma cells

A series of the half-sandwich Ir(III) and Rh(III) complexes [M(η5-Cpx)(dpa)X]PF6 (M = Ir for 1–6 and Rh for 7–12) containing N-(pyridin-2-yl)pyridin-2-amine (2,2′-dipyridylamine, dpa), pentamethylcyclopentadienyl (Cp*; for 1–5 and 7–11) or 1,2,3,4-tetramethyl-5-phenylcyclopentadienyl (Cpph; for 6 and 12) ring, and various monodentate ligands (X), specifically Cl− (for 1, 6, 7 and 12), Br− (for 2 and 8), I− (for 3 and 9), valproato (VP; for 4 and 10) or 4-phenylbutyrato (PB; for 5 and 11), was prepared. The complexes were thoroughly characterized by elemental analysis, IR and NMR spectroscopy and mass spectrometry. A single-crystal X-ray analysis was performed for complex [Ir(η5-Cpph)(dpa)Cl]PF6 (6), revealing a pseudo-octahedral piano-stool geometry with a bidentate N,N′-coordinated dpa ligand, a penta-hapto coordinated Cpph ring and a monodentate chlorido ligand. The crystal structure of complex 6 is stabilized by N–H⋯F, C–H⋯F, C–H⋯Cl, C–H⋯C and C⋯F non-covalent contacts. Complexes 1–12 were screened for their in vitro cytotoxicity against the A2780 human ovarian carcinoma cell line. The best-performing iridium(III) complex 6 showed markedly higher activity (IC50 = 23.5 μM) than complexes 1–3, 5, 9 and 12, whose IC50 ranged from 68.7 to 87.1 μM. Iridium(III) complex 4 and rhodium(III) complexes 7, 8, 10 and 11 were inactive against the A2780 cells in the tested concentration range (IC50 > 100.0 μM). The chlorido complexes 1, 6, 7 and 12 were studied by 1H NMR spectroscopy for their hydrolytic stability in the 20% DMF-d7/80% D2O and 20% MeOD-d4/80% D2O mixture of solvents, revealing Ir(III) complexes 1 and 6 as stable, while Rh(III) complexes 7 and 12 partially hydrolysed in the used medium. Moreover, hydrophobicity (lipophilicity) of complexes 1–12 was studied by an octanol/water partition (logP).

LncRNA snaR upregulates GRB2-associated binding protein 2 and promotes proliferation of ovarian carcinoma cells

BackgroundThe functionality of lncRNA snaR has only been characterized in breast cancer and colon cancer. The aim of the current study is to explore the involvement of lncRNA snaR in ovarian carcinoma (OC). Materials and methodsExpression of lncRNA snaR and GRB2-associated binding protein 2 (GAB2) in plasma of both patients with OC and healthy females was detected by qRT-PCR. Application value of plasma lncRNA snaR in the diagnosis of OC was evaluated by ROC analysis. Correlation between plasma lncRNA snaR and GAB2 was analyzed by Pearson correlation coefficient. LncRNA snaR and GAB2 expression vectors as well as GAB2 siRNA were transfected into cells of human OC cell lines, and the effect on lncRNA snaR expression, GAB2 expression and cell proliferation was detected by qRT-PCR, western blot and CCK-8 assay. ResultsIt was observed that plasma levels of lncRNA snaR and GAB2 were significantly higher in OC patients than those in healthy controls. In effect, high levels of plasma lncRNA snaR and GAB2 distinguished OC patients from healthy controls. Plasma lncRNA snaR and GAB2 were positively correlated in OC patients but not in healthy controls. LncRNA snaR overexpression promoted cancer cell proliferation and upregulated GAB2 expression. ConclusionsGAB2 overexpression also promoted cancer cell proliferation but showed no significant effects on lncRNA snaR expression, while GAB2 siRNA silencing significantly attenuated the enhancing effects of lncRNA snaR overexpression on cancer cell proliferation. LncRNA snaR may promote proliferation of ovarian carcinoma cells by upregulating GAB2 expression.

Establishment and molecular characterization of a human ovarian clear cell carcinoma cell line (FDOV1)

BackgroundOvarian clear cell carcinoma is a distinct histologic subtype with grave survival. The underlying molecular mechanism is not fully elucidated. However, we don’t have many cell lines, which are useful experimental tools for research. We describe the establishment and characterization of a new ovarian clear cell carcinoma cell line from a Chinese patient.ResultsFDOV1 has been subcultured for more than 80 generations. Monolayer cultured cells are polygonal in shape, showing a transparent cytoplasm full of vacuoles. The number of chromosomes ranges from 45 to 90. FDOV1 cells produces CA-125, but not CA-199. The cells could be transplanted and produced tumors mimicking the donor tumor morphologically and immunohistochemically. Whole exome sequence showed both FDOV1 and tissue block harbored PIK3CA H1047R mutation and ARID1A frameshift mutations (p.L2106 fs, p.N201 fs). More interestingly, we observed SPOP mutation (p.D82H) and ZNF217 (chromosome 20q13) amplification in FDOV1, which are quite novel.ConclusionsOnly a few patient-derived ovarian clear cell carcinoma cell lines have been reported in the literature. FDOV1 is the very first one, to the best of our knowledge, from a Mainland Chinese patient. It showed infinite multiplication until now and tumorigenicity in vivo. FDOV1 has co-existing PIK3CA and ARID1A mutations. It also harbored SPOP mutation and ZNF217 amplification, which would probably be a good model for exploring the molecular mechanism of ovarian clear cell carcinoma.