scholarly journals Biotin-streptavidin-guided two-step pretargeting approach using PLGA for molecular ultrasound imaging and chemotherapy for ovarian cancer

PeerJ ◽  
2021 ◽  
Vol 9 ◽  
pp. e11486
Author(s):  
Hang Zhou ◽  
Jing Fu ◽  
Qihuan Fu ◽  
Yujie Feng ◽  
Ruixia Hong ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Ultrasound Imaging ◽  
High Performance ◽  
Encapsulation Efficiency ◽  
Plga Nanoparticles ◽  
Cell Counting ◽  
Ovarian Cancer Cells ◽  
Skov3 Cells ◽  
Targeting Ability ◽  
Targeting Strategy

Background Ovarian cancer seriously threatens the lives and health of women, and early diagnosis and treatment are still challenging. Pre-targeting is a promising strategy to improve the treatment efficacy of ovarian cancer and the results of ultrasound imaging. Purpose To explore the effects of a pre-targeting strategy using streptavidin (SA) and paclitaxel (PTX)-loaded phase-shifting poly lactic-co-glycolic acid (PLGA) nanoparticles with perfluoro-n-pentane (PTX-PLGA-SA/PFPs) on the treatment and ultrasound imaging of ovarian cancer. Methods PTX-PLGA/PFPs were prepared with a single emulsion (O/W) solvent evaporation method and SA was attached using carbodiimide. The encapsulation efficiency of PTX and the release characteristics were assessed with high performance liquid chromatography. The phase-change characteristics of the PTX-PLGA-SA/PFPs were investigated. The anti-carcinoembryonic antigen (CEA) antibody (Ab) was covalently attached to PTX-PLGA/PFPs via carbodiimide to create PTX-PLGA-Ab/PFPs. The targeting efficiency of the nanoparticles and the viability of ovarian cancer SKOV3 cells were evaluated in each group using a microscope, flow cytometry, and cell counting kit 8 assays. Results THE PTX-PLGA-SA/PFPs were spheres with a size of 383.0 ± 75.59 nm. The encapsulation efficiency and loading capability of the nanoparticles for PTX were 71.56 ±  6.51% and 6.57 ± 0.61%, respectively. PTX was burst-released up to 70% in 2–3 d. When irradiated at 7.5 W for 3 min, the PTX-PLGA-SA/PFPs visibly enhanced the ultrasonography images (P < 0.05). At temperatures of 45°C and 60°C the nanoparticles phase-shifted into micro-bubbles and the sizes increased. The binding efficiencies of SA and Ab to the PTX-PLGA/PFPs were 97.16 ±  1.20% and 92.74 ± 5.75%, respectively. Pre-targeting resulted in a high binding efficacy and killing effect on SKOV3 cells (P < 0.05). Conclusions The two-step pre-targeting process can significantly enhance the targeting ability of PTX-loaded PLGA nanoparticles for ovarian cancer cells and substantially improve the therapeutic efficacy. This technique provides a new method for ultrasonic imaging and precise chemotherapy for ovarian cancer.

scholarly journals Hedgehog−Gli2 Signaling Promotes Chemoresistance in Ovarian Cancer Cells by Regulating MDR1

2022 ◽  
Vol 11 ◽  
Author(s):  
Qian Wang ◽  
Xin Wei ◽  
Lanyan Hu ◽  
Lingling Zhuang ◽  
Hong Zhang ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Nude Mice ◽  
Chemotherapy Resistance ◽  
Cell Counting ◽  
Luciferase Reporter ◽  
Ovarian Cancer Cells ◽  
Luciferase Reporter Gene ◽  
Downstream Target ◽  
Skov3 Cells

BackgroundCisplatin (DDP) resistance remains a key challenge in improving the clinical outcome of patients with ovarian cancer (OC). Gli2 overexpression can lead to DDP resistance in OC cells, but the specific underlying regulatory mechanism remains unclear. The membrane transporter encoding gene MDR1 positively regulates chemotherapy resistance in various cancer types. We evaluated MDR1 as a potential Gli2 downstream target and the contribution of the Gli2/MDR1 axis in promoting DDP resistance in OC cells.MethodsTo generate drug-resistant SKOV3/DDP cells, SKOV3 cells were grown for six months under continuous induction wherein the DDP concentration was steadily increased. Gli2 expression in OC cells with varying DDP sensitivities was detected using western blot. Cell counting kit-8 assays were used to assess the DDP sensitivity of SKOV3, SKOV3/DDP, A2780, and A2780/DDP cells and reversal of DDP resistance in SKOV3/DDP and A2780/DDP cells. Cell proliferation was analyzed using 5-ethynyl-2′-deoxyuridine (EdU) incorporation assays. The transcriptional regulation of MDR1 by Gli2 was determined using luciferase reporter assays. Finally, xenograft OC tumors were generated in nude mice, which were then treated with intraperitoneal DDP or phosphate-buffered saline (PBS) injections to investigate if Gli2 affected DDP resistance in OC in vivo.ResultsDDP-resistant SKOV3/DDP and A2780/DDP cells showed higher expression of Gli2 and MDR1 as compared with that in DDP-sensitive OC cells. Gli2 knockdown in SKOV3/DDP cells significantly reduced MDR1 expression, whereas it increased DNA damage, thereby sensitizing OC cells to DDP. Similar results were obtained after targeting Gli2 expression with the Gli-antagonist 61 inhibitor (GANT61) in SKOV3/DDP and A2780/DDP cells. In cells stably overexpressing Gli2, treatment with gradient concentrations of verapamil, an MDR1 inhibitor, significantly inhibited MDR1 expression. Our findings indicate that downregulation of MDR1 expression may reverse OC cell resistance to DDP. Moreover, dual-luciferase reporter gene assays confirmed that MDR1 is a direct downstream target of Gli2, with Gli2 positively regulating MDR1 expression. Finally, subcutaneous xenotransplantation in nude mice demonstrated that Gli2 plays a key role in regulating OC drug resistance.ConclusionsWe identified a mechanism by which Hedgehog-Gli signaling regulates OC chemoresistance by modulating MDR1 expression. Hence, Gli2 and MDR1 are potential biomarkers and therapeutic targets in patients with chemoresistant OC.

scholarly journals The ABCB1 3435C > T polymorphism influences docetaxel transportation in ovarian cancer

2019 ◽  
Vol 47 (10) ◽  
pp. 5256-5269 ◽  
Author(s):  
Beibei Yin ◽  
Ping Lu ◽  
Jing Liang ◽  
Wei Zhang ◽  
Meng Xin ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
High Performance ◽  
Ovarian Cancer Cells ◽  
Wild Type ◽  
Nucleotide Polymorphism ◽  
Single Nucleotide ◽  
Docetaxel Resistance ◽  
Atp Binding Cassette Transporter ◽  
Skov3 Cells ◽  
Transmembrane Resistance

Objective To investigate the effect of the ATP-binding cassette transporter superfamily B member 1 gene ( ABCB1) 3435C > T single nucleotide polymorphism (SNP) on docetaxel transportation in ovarian cancer cells. Methods ES-2 and SKOV3 cells were transfected with an ABCB1 3435C > T recombinant plasmid, and mRNA expression was detected by real-time PCR. The MTT assay was used to detect the toxicity of docetaxel. High-performance liquid chromatography determined the drug concentration in different cell models to evaluate intracellular accumulation, and a transmembrane resistance experiment was used to assess permeability and evaluate the effect of P-gp activity on drug transportation. A tumor-bearing mouse model was established to evaluate the effect of ABCB1 3435C > T on docetaxel resistance. Results P-gp was overexpressed in cells transfected with the ABCB1 3435C > T plasmid, leading to a significant increase in drug resistance to docetaxel. ABCB1 3435C/wild-type transfection significantly promoted the transport of docetaxel mediated by P-gp compared with ABCB1 3435T/mutant transfection. Conclusion P-gp encoded by the ABCB1 variant allele appears to be more efficient at transporting docetaxel compared with the wild-type allele. The ABCB1 3435C > T SNP dramatically affected the efflux ability of P-gp against docetaxel, and may influence P-gp expression and activity.

scholarly journals Synthesis of Ag@Fe3O4 Nanoparticles for Photothermal Treatment of Ovarian Cancer

2019 ◽  
Vol 2019 ◽  
pp. 1-6 ◽  
Author(s):  
Bing Liu ◽  
Jian Zhou ◽  
Bin Zhang ◽  
Jing Qu
Keyword(s):  
Ovarian Cancer ◽  
Cancer Cells ◽  
Laser Irradiation ◽  
Near Infrared ◽  
Cell Counting ◽  
Photothermal Effect ◽  
Ovarian Cancer Cells ◽  
Photothermal Treatment ◽  
Skov3 Cells ◽  
Nir Laser

Photothermal therapy is a promising approach for cancer treatment. In our study, we investigate the photothermal effect of different concentrations of the Ag@Fe3O4 nanoparticles on apoptosis and proliferation in the human epithelial ovarian cancer cells SKOV3. Ovarian cancer cells SKOV3 were treated with the Ag@Fe3O4 nanoparticles under an 808 nm near-infrared (NIR) laser irradiation at different concentrations. The cell proliferation was measured by the cell counting kit-8 (CCK-8) assay. The results show that the Ag@Fe3O4 nanoparticles with NIR laser irradiation could markedly inhibit the proliferation of the ovarian cancer cells SKOV3 independent of a concentration-time manner. Meanwhile, the cell morphology was also seriously damaged under the treatment of high-concentration nanoparticles. However, Ag@Fe3O4 nanoparticles have almost no obvious effect on the growth of SKOV3 cells without NIR laser illumination treatment. Therefore, it is reasonable to believe that the Ag@Fe3O4 nanoparticles have promising applications in photothermal treatment of cancer cells.

scholarly journals MiR-200c-3p Contrasts PD-L1 Induction by Combinatorial Therapies and Slows Proliferation of Epithelial Ovarian Cancer through Downregulation of β-Catenin and c-Myc

Cells ◽  
2021 ◽  
Vol 10 (3) ◽  
pp. 519
Author(s):  
Eleni Anastasiadou ◽  
Elena Messina ◽  
Tiziana Sanavia ◽  
Lucia Mundo ◽  
Federica Farinella ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Epithelial Ovarian Cancer ◽  
Therapeutic Strategy ◽  
Target Genes ◽  
Ovarian Cancer Cells ◽  
Oncogenic Signaling ◽  
Experimental Conditions ◽  
Skov3 Cells ◽  
In Silico Analyses ◽  
Post Therapy

Conventional/targeted chemotherapies and ionizing radiation (IR) are being used both as monotherapies and in combination for the treatment of epithelial ovarian cancer (EOC). Several studies show that these therapies might favor oncogenic signaling and impede anti-tumor responses. MiR-200c is considered a master regulator of EOC-related oncogenes. In this study, we sought to investigate if chemotherapy and IR could influence the expression of miR-200c-3p and its target genes, like the immune checkpoint PD-L1 and other oncogenes in a cohort of EOC patients’ biopsies. Indeed, PD-L1 expression was induced, while miR-200c-3p was significantly reduced in these biopsies post-therapy. The effect of miR-200c-3p target genes was assessed in miR-200c transfected SKOV3 cells untreated and treated with olaparib and IR alone. Under all experimental conditions, miR-200c-3p concomitantly reduced PD-L1, c-Myc and β-catenin expression and sensitized ovarian cancer cells to olaparib and irradiation. In silico analyses further confirmed the anti-correlation between miR-200c-3p with c-Myc and β-catenin in 46 OC cell lines and showed that a higher miR-200c-3p expression associates with a less tumorigenic microenvironment. These findings provide new insights into how miR-200c-3p could be used to hold in check the adverse effects of conventional chemotherapy, targeted therapy and radiation therapy, and offer a novel therapeutic strategy for EOC.

scholarly journals Dasatinib (BMS-35482) Interacts Synergistically With Docetaxel, Gemcitabine, Topotecan, and Doxorubicin in Ovarian Cancer Cells With High SRC Pathway Activation and Protein Expression

2014 ◽  
Vol 24 (2) ◽  
pp. 218-225 ◽  
Author(s):  
Angeles Alvarez Secord ◽  
Deanna Teoh ◽  
Jingquan Jia ◽  
Andrew B. Nixon ◽  
Lisa Grace ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Protein Expression ◽  
Cancer Cells ◽  
Combination Index ◽  
Chemotherapeutic Agents ◽  
Cytotoxic Agents ◽  
Ovarian Cancer Cells ◽  
Response Curves ◽  
Pathway Activation ◽  
Skov3 Cells

PurposeThis study aimed to explore the activity of dasatinib in combination with docetaxel, gemcitabine, topotecan, and doxorubicin in ovarian cancer cells.MethodsCells with previously determined SRC pathway and protein expression (SRC pathway/SRC protein IGROV1, both high; SKOV3, both low) were treated with dasatinib in combination with the cytotoxic agents. SRC and paxillin protein expression were determined pretreatment and posttreatment. Dose-response curves were constructed, and the combination index (CI) for drug interaction was calculated.ResultsIn the IGROV1 cells, dasatinib alone reduced phospho-SRC/total SRC 71% and p-paxillin/t-paxillin ratios 77%. Phospho-SRC (3%–33%; P = 0.002 to 0.04) and p-paxicillin (6%–19%; P = 0.01 to 0.05) levels were significantly reduced with dasatinib in combination with each cytotoxic agent. The combination of dasatinib and docetaxel, gemcitabine, or topotecan had a synergistic antiproliferative effect (CI, 0.49–0.68), whereas dasatinib combined with doxorubicin had an additive effect (CI, 1.08).In SKOV3 cells, dasatinib resulted in less pronounced reductions of phospho-SRC/total SRC (49%) and p-paxillin/t-paxillin (62%). Phospho-SRC (18%; P < 0.001) and p-paxillin levels (18%; P = 0.001; 9%; P = 0.007) were significantly decreased when dasatinib was combined with docetaxel and topotecan (p-paxillin only). Furthermore, dasatinib combined with the cytotoxics in the SKOV3 cells produced an antagonistic interaction on the proliferation of these cells (CI, 1.49–2.27).ConclusionsDasatinib in combination with relapse chemotherapeutic agents seems to interact in a synergistic or additive manner in cells with high SRC pathway activation and protein expression. Further evaluation of dasatinib in combination with chemotherapy in ovarian cancer animal models and exploration of the use of biomarkers to direct therapy are warranted.

Gemcitabine Nanoparticles Improve the Activity of Ovarian Cancer Cells by Inhibiting CA-125 and Apoptosis-Related Proteins

2021 ◽  
Vol 11 (7) ◽  
pp. 1400-1405
Author(s):  
Sisi Yi ◽  
Chen Feng ◽  
Xiaohua Hu
Keyword(s):  
Ovarian Cancer ◽  
Cell Viability ◽  
Release Rate ◽  
Inhibitory Action ◽  
Encapsulation Efficiency ◽  
Slow Release ◽  
Drug Loading ◽  
Ca 125 ◽  
Ovarian Cancer Cells ◽  
Related Proteins

In recent years, the risk of ovarian cancer (OC) has become increasingly prevalent. Gemcitabine (GE) provides excellent inhibitory action on some solid tumors, but how it affects OC remains elusive. In the present research, we prepared GE nanoparticles (GEN) and analyzed OC cell viability under its intervention, hoping to conceive novel ideas for future clinical treatment of OC. Through experiments, we observed that the encapsulation efficiency and drug loading of GEN were observably higher than those of GE alone, and the release rate presented a stable slow release state. Under GEN intervention, the viability of OC cells was decreased, the apoptosis rate was elevated, and the apoptosis-related proteins were activated, while CA-125 was suppressed. Therefore, we can see that GEN exert favorable inhibitory action on OC cell viability, whose mechanism may be achieved through activating apoptosis-related proteins and inhibiting CA-125, which may be a new scheme for OC treatment in the future.

GRP137 promotes cell proliferation and metastasis through regulation of the PI3K/AKT pathway in human ovarian cancer

2018 ◽  
Vol 104 (5) ◽  
pp. 330-337 ◽  
Author(s):  
Li-qian Zhang ◽  
Su-qing Yang ◽  
Xiang-dong Qu ◽  
Xian-jun Chen ◽  
Hong-sheng Lu ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
G Protein ◽  
Biological Activities ◽  
Xenograft Model ◽  
Akt Pathway ◽  
Ovarian Cancer Cells ◽  
Human Ovarian Cancer ◽  
G Protein Coupled Receptor ◽  
Skov3 Cells ◽  
G Protein Coupled

Purpose: Ovarian cancer is one of the leading causes of death for women worldwide. The present study aims to investigate the role of G protein-coupled receptor 137 (GPR137) in the biological activities of ovarian cancer cells. Methods: (QUERY: Please supply Methods for Abstract) Results: G protein-coupled receptor 137 was highly expressed in clinical ovarian cancer tissues and exhibited the highest protein levels in SKOV3 cells and OVCAR3 cells. Knockdown of GPR137 caused significant decreases in cell proliferative rates and colony formation abilities in SKOV3 cells and OVCAR3 cells and also inhibited the in vivo tumorigenesis in a xenograft model. It was observed that knockdown of GPR137 inhibited cell motility by up to 40% in SKOV3 cells and approximately 65% in OVCAR3 cells in wound-healing assay. Cell migration abilities were consistently inhibited by 68.2% in SKOV3 cells and 59.3% in OVCAR3 cells, whereas cell invasion abilities were inhibited by 64.0% and 74.2% in SKOV3 and OVCAR3 cells, respectively, after knockdown of GPR137. When GPR137 was depleted, epithelial markers were increased, while mesenchymal markers decreased. Conclusions: Our data suggest that GPR137 plays pro-oncogenic roles in ovarian cancer via regulation of the PI3K/AKT pathway. These observations might pave new insights into therapeutic strategies against human ovarian cancer.

Knockdown of BAG3 synergizes with olaparib to kill ovarian cancer cells via repressing autophagy

2020 ◽  
pp. jim-2020-001602
Author(s):  
Kexin Wang ◽  
Jianhua Zheng
Keyword(s):  
Ovarian Cancer ◽  
Western Blot ◽  
Transfection Efficiency ◽  
Parp Inhibitor ◽  
Beclin 1 ◽  
Cell Counting ◽  
Ovarian Cancer Cells ◽  
Western Blot Assay ◽  
Related Proteins

This study aimed at expounding the synergistic effect of Bcl-2-associated athanogene 3 (BAG3) knockdown and poly ADP-ribose polymerase (PARP) inhibitor on ovarian cancer (OC) cells and the potential mechanism. Short hairpin RNA (shRNA) targeting BAG3 (sh-BAG3) was transfected into SK-OV-3 (SKOV-3 ;SKOV3) and A2780 cells, and western blot assay was used to detect transfection efficiency. Cell proliferation and apoptosis were detected by the cell counting kit-8 method, 5-Bromodeoxyuridine (BrdU) experiment and flow cytometry analysis, respectively. The expressions of apoptosis-related proteins Bax and Bcl-2, as well as the expressions of autophagy-related proteins LC3-I, LC3-II and Beclin-1, were examined by western blot assay. Additionally, the cells were treated with autophagy activator rapamycin to investigate whether the tumor-suppressive function of BAG3 knockdown+PARP inhibitor was dependent on autophagy. In this work, we demonstrated that BAG3 knockdown further sensitized OC cells to olaparib treatment, reducing cellular viability and promoting apoptosis. Both sh-BAG3 and olaparib decreased the expression of Beclin-1 and the LC3-Ⅱ:LC3-I ratio, and their synergism further inhibited the process of autophagy. However, the aforementionede effects were reversed after the cells were treated with rapamycin. Based on these results, we concluded that BAG3 knockdown synergizes with olaparib to kill OC cells in vitro by repressing autophagy.

PLGA-nanoparticles loaded with a thiosemicarbazone derived palladium(ii) complex as a potential agent to new formulations for human ovarian carcinoma treatment

2020 ◽  
Vol 44 (35) ◽  
pp. 14928-14935
Author(s):  
Carolina G. Oliveira ◽  
Luciana F. Dalmolin ◽  
R. T. C. Silva ◽  
Renata F. V. Lopez ◽  
Pedro I. S. Maia ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Cell Viability ◽  
Ovarian Carcinoma ◽  
Cancer Cells ◽  
Plga Nanoparticles ◽  
Cytotoxic Agent ◽  
Ovarian Cancer Cells ◽  
Ovarian Cell ◽  
Encapsulation Process ◽  
Human Ovarian Carcinoma

The encapsulation process of the PdII complex [PdCl(PPh3)(PrCh)], a promising cytotoxic agent on ovarian cancer cells, in PLGA polymer was studied. The cytotoxicity results showed that the formulation led to a significant reduction of the ovarian cell viability (80% at 1 μM).

scholarly journals Differential induction of LRP16 by liganded and unliganded estrogen receptor α in SKOV3 ovarian carcinoma cells

2009 ◽  
Vol 202 (1) ◽  
pp. 167-177 ◽  
Author(s):  
Liyuan Tian ◽  
Zhiqiang Wu ◽  
Yali Zhao ◽  
Yuanguang Meng ◽  
Yiling Si ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Estrogen Receptor ◽  
Cancer Cells ◽  
Estrogen Receptor Α ◽  
Ovarian Cancer Cells ◽  
Induction Effect ◽  
Skov3 Cell ◽  
Signaling Transduction ◽  
Estrogen Response ◽  
Skov3 Cells

Previously, we investigated the induction effect of LRP16 expression by estrogen (17β-estradiol, E2) and established a feed-forward mechanism that activated estrogen receptor α (ERα) transactivation in estrogen-dependent epithelial cancer cells. LRP16 is required for ERα signaling transduction by functioning as an ERα coactivator. In this study, we demonstrated that LRP16 expression was upregulated in E2-responsive BG-1 ovarian cancer cells, but was downregulated in estrogen-resistant SKOV3 ovarian cancer cells. Pure estrogen antagonist ICI 182 780 did not affect LRP16 expression in SKOV3 cell. The unliganded ERα upregulated LRP16 expression and enhanced LRP16 promoter activity in SKOV3 cells; however, this induction was blocked by estrogen stimulation. Results from chromatin immunoprecipitation experiment revealed a strong recruitment of the unliganded ERα at LRP16 promoter in the absence of estrogen; however, ERα was largely released from the DNA upon E2 stimulation. Modulation in LRP16 expression level did not significantly change the proliferation rate of SKOV3 cells and the growth responsiveness of cells to E2. Knockdown of LRP16 by RNA interference in SKOV3 cells markedly attenuated estrogen response element-dependent ERα reporter gene activity and E2-induced c-Myc expression. Our study suggests a novel mechanism of estrogen resistance of ovarian cancer by which estrogen-repressed signaling pathway antagonizes estrogen-activated signaling transduction.

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