scholarly journals Ultrasound-Targeted Microbubble Destruction-Mediated Inhibition of Livin Expression Accelerates Ovarian Cancer Cell Apoptosis

2021 ◽  
Vol 2021 ◽  
pp. 1-7
Author(s):  
Xiaolin Xu ◽  
Shuqin Yu ◽  
Xiaoyuan Liu ◽  
Ying Feng
Keyword(s):  
Ovarian Cancer ◽  
Protein Expression ◽  
Cancer Cell ◽  
Cell Apoptosis ◽  
Caspase 3 ◽  
Ovarian Cancer Cell ◽  
Ovarian Cancer Cells ◽  
Caspase 8 ◽  
Expression Levels ◽  
Mrna And Protein Expression

Objective. Ultrasound-targeted microbubble destruction (UTMD) technique has recently been developed as a nonviral delivery of gene therapy. This study aimed at investigating the survival and apoptosis of ovarian cancer cell line OVCA-433 by inhibiting Livin expression through ultrasound-targeted microbubble destruction. Methods. We synthesized a targeted microbubble agent for UTMD-mediated shRNA against Livin gene in human ovarian cancer OVCA-433 cells. Lipid microbubbles were conjugated with a luteinizing hormone-releasing hormone analog (LHRHa) by an avidin-biotin linkage to target the ovarian cancer OVCA-433 cells expressing LHRH receptors. The microbubbles were mixed with the recombinant plasmid harboring shRNA-Livin. shRNA-Livin was transfected into OVCA-433 cells upon exposure to 1 MHz pulsed ultrasound beam (0.5 W/cm2) for 8 s. Cell survival was measured by the MTT assay, cell apoptosis by flow cytometry using annexin V/PI double staining, and cell ultrastructure by using the transmission electron microscope. The mRNA and protein expression levels of caspase-3 and caspase-8 were detected by RT-qPCR and western blotting. Results. UTMD-mediated delivery of shRNA-Livin remarkably reduced the survival of OVCA-433 cells but promoted the apoptosis compared with shRNA-Livin alone, shRNA-Livin plus nontargeted microbubbles, and shRNA-Livin plus LHRHa-conjugated microbubbles containing shRNA-Livin with or without exposure to ultrasound pulses. It was also found that UTMD-mediated delivery of shRNA-Livin notably declined the mRNA and protein expression levels of caspase-3 and caspase-8 in OVCA-433 cells compared with shRNA-Livin alone, shRNA-Livin plus nontargeted microbubbles, and shRNA-Livin plus LHRHa-conjugated microbubbles containing shRNA-Livin with or without exposure to ultrasound pulses. Conclusion. Our experiment verifies the hypothesis that ultrasound mediation of targeted microbubbles can enhance the transfection efficiency of shRNA-Livin in ovarian cancer cells.

MiR-203 Regulates DJ-1/Phosphatase and Tensin Homologue Deleted on Chromosome Ten/Phosphatidylinositol-3 Kinase/Protein Kinase B Pathway and Affects Proliferation, Apoptosis and Cisplatin Resistance of Ovarian Cancer Cells

2020 ◽  
Vol 10 (1) ◽  
pp. 76-80
Author(s):  
Ping Liu ◽  
Jie Wen ◽  
Nannan Zhao
Keyword(s):  
Ovarian Cancer ◽  
Protein Expression ◽  
Cancer Cells ◽  
Cancer Cell ◽  
Cell Apoptosis ◽  
Ovarian Cancer Cell ◽  
Resistant Cell ◽  
Resistant Cell Line ◽  
Ovarian Cancer Cells ◽  
Skov3 Cells

DJ-1 negatively regulates PTEN and plays a role in tumorigenesis and progression. Abnormal miR-203 expression is associated with ovarian cancer. miR-203 was predicted to have a relationship with DJ-1 3-UTR. Our study assessed miR-203’s role in ovarian cancer cell cisplatin (CDDP) resistance. The CDDP-resistant cell line SKOV3/CDDP was established and compared with the expression of miR-203 and DJ-1 in the parental SKOV3 cells. SKOV3/CDDP cells were separated into miR-NC group and miR-203 mimic group followed by analysis of DJ-1, PTEN and p-AKT expression, cell apoptosis and proliferation. There was a targeted relationship between miR-203 and DJ-1 mRNA. miR-203 and PTEN protein expression in SKOV3/CDDP cells was significantly reduced compared to SKOV3 cells with significantly upregulated DJ-1. miR-203 mimic significantly upregulated miR-203, decreased DJ-1 and p-AKT protein expression and elevated PTEN expression along with increased cell apoptosis and reduced cell proliferative ability. Decreased miR-203 expression and increased DJ-1 expression participate in drug resistance in ovarian cancer cells. miR-203 inhibits DJ-1 expression, affects PTEN-PI3K/AKT signaling, inhibits ovarian cancer cell proliferation and promotes apoptosis, and reduces CDDP resistance.

scholarly journals Anticancer effect of 7-hydroxycoumarin in cisplatin-resistant ovarian cancer cell is mediated via apoptosis induction, caspase activation and cell cycle arrest at G2M phase

2022 ◽  
Vol 20 (2) ◽  
pp. 281-286
Author(s):  
Hongmei Wang ◽  
Yina Wang
Keyword(s):  
Cell Cycle ◽  
Ovarian Cancer ◽  
Cell Proliferation ◽  
Cancer Cells ◽  
Cancer Cell ◽  
Cell Apoptosis ◽  
Ovarian Cancer Cell ◽  
Ovarian Cancer Cells ◽  
Anticancer Effect ◽  
Cycle Arrest

Purpose: To investigate the anticancer effects of 7-hydroxycoumarin against cisplatin-resistant ovarian cancer cell line, and the underlying mechanism(s). Methods: Cell proliferation was determined using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay. The 4’,6-diamidino-2-phenylindole (DAPI) and acridine orange/ethidium bromide (AO/EB) dual staining methods were used for measuring cell apoptosis in terms of DNA damage. Flow cytometry was used for analysis of mitosis of cancer cells, while protein expression levels were assayed with western blotting. Results: The 7-hydroxycoumarin preferentially inhibited the proliferation of the ovarian cancer cells, but had significantly less prominent effects on normal cells (p < 0.05). The decrease in cell proliferation was due to induction of cell apoptosis via caspase-linked apoptotic pathway. Treatment with 7- hdoxycoumarin further led to the arrest of cancer cell cycle at G2/M stage (p < 0.05) via down-regulation of the expressions of regulatory proteins that promote mitotic entry. Conclusion: 7-Hydroxycoumarin exerts significant anticancer effect against cisplatin-resistant ovarian cancer cells via decrease in cell proliferation, induction of apoptosis and mitotic cell cycle arrest. Thus, the compound could emerge as a vital lead molecule in the treatment of cisplatin-resistant type of human ovarian cancer.

miR-194 Inhibits Ovarian Cancer Cell Proliferation and Reduces Cisplatin Resistance by Targeting Yes-Associated Protein

2020 ◽  
Vol 10 (8) ◽  
pp. 1170-1175
Author(s):  
Hao Tang ◽  
Ping Gong ◽  
Ling Tao ◽  
Yurong Hua
Keyword(s):  
Ovarian Cancer ◽  
Cell Proliferation ◽  
Cancer Cell ◽  
Cell Apoptosis ◽  
Ovarian Cancer Cell ◽  
Resistant Cell ◽  
Resistant Cell Line ◽  
Ovarian Cancer Cells ◽  
Cancer Cell Proliferation ◽  
Elevated Expression

Elevated expression of Yes-associated protein (YAP1) is associated with ovarian cancer. Bioinformatics analysis showed a relationship between miR-194 and YAP1. Our study intends to assess whether miR-194 regulates YAP1 expression and affects the proliferation of ovarian cancer cells and CDDP resistance. CDDP-resistant cell line A2780/CDDP was established and the expression of miR-194 and YAP1 in parental A2780 cells and normal ovarian epithelial IOSE80 cells were compared. A2780/CDDP cells were separated into miR-NC group and miR-194 mimic group followed by analysis of miR-194 and YAP1 expression, and cell apoptosis and proliferation by flow cytometry. There was a targeted relationship between miR-194 and YAP1 mRNA. A2780/CDDP cells had the lowest miR-194 expression followed by A2780 cells and IOSE80 cells. In addition, YAP1 level was highest in A2780/CDDP cells followed by A2780 cells and IOSE80 cells. Compared with miR-NC group, miR-194 expression was significantly increased in miR-194 mimic transfection group and YAP1 protein expression was significantly decreased, with increased cell apoptosis and reduced cell proliferation ability. Decreased miR-194 expression and increased YAP1 expression are related to ovarian cancer CDDP resistance. Increased miR-194 can down-regulate YAP1, inhibit ovarian cancer cell proliferation, promote cell apoptosis, and reduce CDDP resistance.

scholarly journals Stigmasterol Causes Ovarian Cancer Cell Apoptosis by Inducing Endoplasmic Reticulum and Mitochondrial Dysfunction

Pharmaceutics ◽  
2020 ◽  
Vol 12 (6) ◽  
pp. 488 ◽  
Author(s):  
Hyocheol Bae ◽  
Gwonhwa Song ◽  
Whasun Lim
Keyword(s):  
Ovarian Cancer ◽  
Cell Migration ◽  
Cancer Cells ◽  
Cancer Cell ◽  
Cell Apoptosis ◽  
Ovarian Cancer Cell ◽  
Endometrial Adenocarcinoma ◽  
Ovarian Cancer Cells ◽  
Human Ovarian Cancer ◽  
Migration Assay

Background: Phytosterols have physiological effects and are used as medicines or food supplements. Stigmasterol has shown anticancer effects against various cancers such as hepatoma, cholangiocarcinoma, gall bladder carcinoma, endometrial adenocarcinoma and skin, gastric, breast, prostate, and cervical cancer. However, there are no reports on stigmasterol’s effects on ovarian cancer. Methods: We investigated the effects of stigmasterol on proapoptotic signals, mitochondrial function, reactive oxygen species production, and the cytosolic and mitochondrial calcium levels in human ovarian cancer cells, to understand the mechanisms underlying the effects of stigmasterol on ovarian cancer cells. We also conducted migration assay to confirm whether that stigmasterol inhibits ovarian cancer cell migration. Results: Stigmasterol inhibited development of human ovarian cancer cells. However, it induced cell apoptosis, ROS production, and calcium overload in ES2 and OV90 cells. In addition, stigmasterol stimulated cell death by activating the ER-mitochondrial axis. We confirmed that stigmasterol suppressed cell migration and angiogenesis genes in human ovarian cancer cells. Conclusions: Our findings suggest that stigmasterol can be used as a new treatment for ovarian cancer.

scholarly journals CC Chemokine Ligand 7 Derived from Cancer-Stimulated Macrophages Promotes Ovarian Cancer Cell Invasion

Cancers ◽  
2021 ◽  
Vol 13 (11) ◽  
pp. 2745
Author(s):  
Miran Jeong ◽  
Yi-Yue Wang ◽  
Ju-Yeon Choi ◽  
Myong-Cheol Lim ◽  
Jung-Hye Choi
Keyword(s):  
Ovarian Cancer ◽  
Cancer Cells ◽  
Cancer Cell ◽  
Cell Invasion ◽  
Ovarian Cancer Cell ◽  
Ovarian Cancer Cells ◽  
Human Ovarian Cancer ◽  
Cancer Cell Invasion ◽  
Cc Chemokine ◽  
Chemokine Ligand

In the tumor microenvironment, macrophages have been suggested to be stimulated by tumor cells, becoming tumor-associated macrophages that promote cancer development and progression. We examined the effect of these macrophages on human ovarian cancer cell invasion and found that conditioned medium of macrophages stimulated by ovarian cancer cells (OC-MQs) significantly increased cell invasion. CC chemokine ligand 7 (CCL7) expression and production were significantly higher in OC-MQs than in the control macrophages. Peritoneal macrophages from patients with ovarian cancer showed higher CCL7 expression levels than those from healthy controls. Inhibition of CCL7 using siRNA and neutralizing antibodies reduced the OC-MQ-CM-induced ovarian cancer cell invasion. CC chemokine receptor 3 (CCR3) was highly expressed in human ovarian cancer cells, and a specific inhibitor of this receptor reduced the OC-MQ-CM-induced invasion. Specific signaling and transcription factors were associated with enhanced CCL7 expression in OC-MQs. CCL7-induced invasion required the expression of matrix metalloproteinase 9 via activation of extracellular signal-related kinase signaling in human ovarian cancer cells. These data suggest that tumor-associated macrophages can affect human ovarian cancer metastasis via the CCL7/CCR3 axis.

scholarly journals Structural Bases for the Synergistic Inhibition of Human Thymidylate Synthase and Ovarian Cancer Cell Growth by Drug Combinations

Cancers ◽  
2021 ◽  
Vol 13 (9) ◽  
pp. 2061
Author(s):  
Cecilia Pozzi ◽  
Matteo Santucci ◽  
Gaetano Marverti ◽  
Domenico D’Arca ◽  
Lorenzo Tagliazucchi ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Cell Growth ◽  
Cancer Cell ◽  
Thymidylate Synthase ◽  
Ovarian Cancer Cell ◽  
Ovarian Cancer Cells ◽  
Preclinical Research ◽  
Cancer Cell Growth ◽  
X Ray ◽  
Synergistic Inhibition

Combining drugs represent an approach to efficiently prevent and overcome drug resistance and to reduce toxicity; yet it is a highly challenging task, particularly if combinations of inhibitors of the same enzyme target are considered. To show that crystallographic and inhibition kinetic information can provide indicators of cancer cell growth inhibition by combinations of two anti-human thymidylate synthase (hTS) drugs, we obtained the X-ray crystal structure of the hTS:raltitrexed:5-fluorodeoxyuridine monophosphate (FdUMP) complex. Its analysis showed a ternary complex with both molecules strongly bound inside the enzyme catalytic cavity. The synergistic inhibition of hTS and its mechanistic rationale were consistent with the structural analysis. When administered in combination to A2780 and A2780/CP ovarian cancer cells, the two drugs inhibited ovarian cancer cell growth additively/synergistically. Together, these results support the idea that X-ray crystallography can provide structural indicators for designing combinations of hTS (or any other target)-directed drugs to accelerate preclinical research for therapeutic application.

scholarly journals Extracellular Matrix Proteins Expression Profiling in Chemoresistant Variants of the A2780 Ovarian Cancer Cell Line

2014 ◽  
Vol 2014 ◽  
pp. 1-9 ◽  
Author(s):  
Radosław Januchowski ◽  
Piotr Zawierucha ◽  
Marcin Ruciński ◽  
Michał Nowicki ◽  
Maciej Zabel
Keyword(s):  
Ovarian Cancer ◽  
Extracellular Matrix ◽  
Drug Resistance ◽  
Cell Line ◽  
Cancer Cell ◽  
Ovarian Cancer Cell ◽  
Ovarian Cancer Cell Line ◽  
Cancer Cell Line ◽  
Altered Expression ◽  
Expression Levels

Ovarian cancer is the leading cause of death among gynaecological malignancies. Extracellular matrix (ECM) can affect drug resistance by preventing the penetration of the drug into cancer cells and increased resistance to apoptosis. This study demonstrates alterations in the expression levels of ECM components and related genes in cisplatin-, doxorubicin-, topotecan-, and paclitaxel-resistant variants of the A2780 ovarian cancer cell line. Affymetrix Gene Chip Human Genome Array Strips were used for hybridisations. The genes that had altered expression levels in drug-resistant sublines were selected and filtered by scatter plots. The genes that were up- or downregulated more than fivefold were selected and listed. Among the investigated genes, 28 genes were upregulated, 10 genes were downregulated, and two genes were down- or upregulated depending on the cell line. Between upregulated genes 12 were upregulated very significantly—over 20-fold. These genes included COL1A2, COL12A1, COL21A1, LOX, TGFBI, LAMB1, EFEMP1, GPC3, SDC2, MGP, MMP3, and TIMP3. Four genes were very significantly downregulated: COL11A1, LAMA2, GPC6, and LUM. The expression profiles of investigated genes provide a preliminary insight into the relationship between drug resistance and the expression of ECM components. Identifying correlations between investigated genes and drug resistance will require further analysis.

Lysine-specific demethylase 1 (LSD1) promotes ovarian cancer cell progression by Forkhead box O 3a (FOXO3a) inhibition

2020 ◽  
Vol 10 (4) ◽  
pp. 594-602 ◽  
Author(s):  
Li Liu ◽  
Fuxing Hao ◽  
Anping Wang ◽  
Xiaolan Chen ◽  
Bin Zhang ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Cell Proliferation ◽  
Cancer Cell ◽  
Ovarian Cancer Cell ◽  
Soft Agar ◽  
Ovarian Cancer Cells ◽  
Cancer Cell Growth ◽  
Forkhead Box ◽  
Lysine Specific Demethylase ◽  
Cell Progression

Recently, LSD1 is considered as a possible therapeutic mark for ovarian epithelial cancer (OEC). Though, the underlying molecular mechanism by which LSD1 endorses the oncogenesis of OEC has not been fully understood. Here, we revealed that overexpression of LSD1 downregulated Forkhead box O 3a (FOXO3a), while knockdown or pharmacological inhibition of LSD1 upregulated FOXO3a expression. Specifically, LSD1 interacted with demethylated FOXO3a. The LSD1-demethylated FOXO3a degraded via an ubiquitin-proteasome pathway. Biologically, LSD1 destabilized FOXO3a to abrogate its functions in the suppression of soft agar colony and cell proliferation formation in HO8910 ovarian cancer cells. Knockdown of FOXO3a rescued the restricted cell proliferation by LSD1 downregulation. As a whole, our study clarifies a way in ovarian cancer cell growth through the negative regulation of FOXO3a by LSD1.

scholarly journals miR-214 promotes radioresistance in human ovarian cancer cells by targeting PETN

2017 ◽  
Vol 37 (4) ◽  
Author(s):  
Qin Zhang ◽  
Shuxiang Zhang
Keyword(s):  
Ovarian Cancer ◽  
Ionizing Radiation ◽  
Cell Lines ◽  
Cancer Cell ◽  
Ovarian Cancer Cell ◽  
Cancer Cell Lines ◽  
Ovarian Cancer Cells ◽  
Human Ovarian Cancer ◽  
Ovarian Cancer Cell Lines ◽  
Cancer Tissues

Ovarian cancer is one of the leading causes of death among gynecological malignancies. Increasing evidence indicate that dysregulation of microRNAs (miRNAs) plays an important role in tumor radioresistance. The aim of the present study is to investigate whether microRNA-214 (miR-214) was involved in radioresistance of human ovarian cancer. Here, we showed that miR-214 was significantly up-regulated in ovarian cancer tissues and radioresistance ovarian cancer cell lines. Transfection of miR-214 agomir in radiosensitive ovarian cancer cell lines promoted them for resistance to ionizing radiation, whereas transfection of miR-214 antagomir in radioresistance ovarian cancer cell lines sensitized them to ionizing radiation again. Furthermore, we found miR-214 effectively promoted tumor radioresistance in xenograft animal experiment. Western blotting and quantitative real-time PCR demonstrated that miR-214 negatively regulated PTEN in radioresistance ovarian cancer cell lines and ovarian cancer tissues. Taken together, our data conclude that miR-214 contributes to radioresistance of ovarian cancer by directly targeting PTEN.

scholarly journals Discoidin Domain Receptor 2 Mediates Lysophosphatidic Acid-Induced Ovarian Cancer Aggressiveness

2021 ◽  
Vol 22 (10) ◽  
pp. 5374
Author(s):  
Bo Young Jeong ◽  
Kyung Hwa Cho ◽  
Se-Hee Yoon ◽  
Chang Gyo Park ◽  
Hwan-Woo Park ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Cancer Cell ◽  
Lysophosphatidic Acid ◽  
Cell Invasion ◽  
Ovarian Cancer Cell ◽  
Ovarian Cancer Cells ◽  
Cancer Cell Invasion ◽  
Discoidin Domain Receptor ◽  
Cancer Aggressiveness ◽  
Discoidin Domain Receptor 2

Lysophosphatidic acid (LPA), a bioactive lipid produced extracellularly by autotaxin (ATX), has been known to induce various pathophysiological events, including cancer cell invasion and metastasis. Discoidin domain receptor 2 (DDR2) expression is upregulated in ovarian cancer tissues, and is closely associated with poor clinical outcomes in ovarian cancer patients. In the present study, we determined a critical role and signaling cascade for the expression of DDR2 in LPA-induced ovarian cancer cell invasion. We also found ectopic expression of ATX or stimulation of ovarian cancer cells with LPA-induced DDR2 expression. However, the silencing of DDR2 expression significantly inhibited ATX- and LPA-induced ovarian cancer cell invasion. In addition, treatment of the cells with pharmacological inhibitors of phosphoinositide 3-kinase (PI3K), Akt, and mTOR abrogated LPA-induced DDR2 expression. Moreover, we observed that HIF-1α, located downstream of the mTOR, is implicated in LPA-induced DDR2 expression and ovarian cancer cell invasion. Finally, we provide evidence that LPA-induced HIF-1α expression mediates Twist1 expression to upregulate DDR2 expression. Collectively, the present study demonstrates that ATX, and thereby LPA, induces DDR2 expression through the activation of the PI3K/Akt/mTOR/HIF-1α/Twist1 signaling axes, aggravating ovarian cancer cell invasion.

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