Combined Therapy for Paclitaxel and Curcumin by Nonionic Surfactant Vesicles Leading to Enhanced Efficacy of Chemotherapy in Ovarian Cancer Cells Through Inhibiting the Serine/threonine Kinase Akt and Nuclear Factor Kappab Activity

Abstract The combination therapy of cytotoxic drugs and chemosensitizing agents encapsulated in nanoparticles has been highlighted as an effective treatment for various cancers. Combination therapy is promising to produce synergistic anticancer effects, to magnify the treatment effect and overcome multidrug resistance. In this investigation, we have studied augmentation of therapeutic efﬁcacy upon c combinational treatment of paclitaxel (PCL) and curcumin (Cur), an inhibitor of nuclear factor kappa B (NF-κB), in OVCAR-3 cell. PCL and Cur were encapsulated in nanoniosome formulations. Then, the effects of nanoniosome formulations on cytotoxicity, expression profile of AKT-1 gene and NF-κB activity were evaluated. The findings showed that nanoniosomes were highly efﬁcient in delivering the PCL and Cur drugs to OVCAR-3 cell. A 3-fold and 3.6-fold reduction in Cur and PCL concentration were measured, respectively, when the Cur and PCL were administered in nanoniosomes compared to free Cur and free PCL solutions in OVCAR-3 cell. Moreover, curcumin could signiﬁcantly increase cell growth inhibition of paclitaxel so that, in presence of NioCur, the IC50 of NioPCL was diminished to ∼2.4 –fold. AKT-1 gene expression studies showed that co-administration of curcumin/paclitaxel nanoniosome formulations caused 91.2% reduction in AKT-1 gene expression compared to control group. On the other hand, this co-administration caused 79.42% reduction in the amount of NF-κB activity and a 4-fold reduction in the activity of the MDR protein pumps in cancer cells compared to the control group. Our findings demonstrate that the combination therapy of PCL with Cur using the nanoniosomes delivery is a promising strategy for breast cancer more effective therapy

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Anti-cancer Effects of Ketoprofen on the Expression of HE4 Gene and Viability of the A2780 Human Ovarian Cancer Cell Line

Jentashapir Journal of Cellular and Molecular Biology ◽

10.5812/jjcmb.112309 ◽

2021 ◽

Vol In Press (In Press) ◽

Author(s):

Maryam Yahyaie ◽

Majid Morovati-Sharifabad ◽

Elham Salehi ◽

Fatemeh Sarkargar ◽

Gholamhosein Pourghanbari

Keyword(s):

Gene Expression ◽

Ovarian Cancer ◽

Cancer Cells ◽

Real Time ◽

Ovarian Cancer Cell Line ◽

Cancer Cell Line ◽

Ovarian Cancer Cells ◽

Control Group ◽

Ovarian Epithelial Cancer ◽

Anti Cancer

Background: Ovarian cancer is the second leading cause of death in Iran compared with other gynecological diseases. Considering the role of cyclooxygenase (COX) enzymes and prostaglandin E2 production in tumor lesions, nonsteroidal anti-inflammatory drugs (NSAIDs) show antitumor properties by inhibiting COX. Furthermore, some compounds can serve as non-selective inhibitors of COX (such as ketoprofen) and prevent cancer development. Human epididymis protein 4 (HE4) is one of the most sensitive tumor markers known in the study of the disease of ovarian epithelial cancer. The expression of HE4 increases in different types of ovarian cancer. Objectives: The aim of this study was to determine the anti-cancer effects of ketoprofen on the viability of ovarian cancer cells and expression of HE4 gene. Methods: To calculate half-maximal inhibitory concentration (IC50), A2780S cells were treated with different concentrations of ketoprofen for 24 hours, then the cells were incubated with appropriate concentrations of IC50 for 24, 48, and 72 hours. Real-time polymerase chain reaction (PCR) was used to measure changes caused by the effect of drugs on HE4 gene expression and analyzed by the 2-ΔΔCT method. Results: The IC50 level of ketoprofen for 24 hours was 583.7 μM. According to real-time PCR results, treatment of cells with ketoprofen reduced HE4 expression. Conclusions: HE4 gene expression decreased in cells treated with ketoprofen compared with the cells in the control group, which proves the anti-cancer activity of ketoprofen and a reduction in the viability of ovarian cancer cells.

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Combination Therapy of Mesenchymal Stromal Cells and Interleukin-4 Attenuates Rheumatoid Arthritis in a Collagen-Induced Murine Model

Cells ◽

10.3390/cells8080823 ◽

2019 ◽

Vol 8 (8) ◽

pp. 823 ◽

Cited By ~ 2

Author(s):

Shaimaa M. Haikal ◽

Nourtan F. Abdeltawab ◽

Laila A. Rashed ◽

Tarek I. Abd El-Galil ◽

Heba A. Elmalt ◽

...

Keyword(s):

Rheumatoid Arthritis ◽

Gene Expression ◽

Combination Therapy ◽

Mesenchymal Stromal Cells ◽

Stromal Cells ◽

Combined Therapy ◽

Knee Joints ◽

Control Group ◽

Mouse Bone Marrow ◽

Group I

Rheumatoid arthritis (RA) is a disease of the joints that causes decreased quality of life. Mesenchymal stromal cells (MSCs) have immunosuppressive properties, with possible use in the treatment of RA. Similarly, interleukin (IL)-4 has been shown as a potential RA treatment. However, their combination has not been explored before. Therefore, this study aimed to investigate the effect of a combination therapy of MSCs and IL-4 in the treatment of RA, using a murine collagen-induced arthritis (CIA) model. Arthritis was induced in Balb/c mice by two intradermal injections of type II collagen (CII), at days 0 and 21. CIA mice were randomly assigned to four groups; group I received an intravenous injection of mouse bone marrow-derived MSCs, while group II received an intraperitoneal injection of IL-4. Group III received a combined treatment of MSC and IL-4, while group IV served as a CIA diseased control group receiving phosphate buffer saline (PBS). A fifth group of healthy mice served as the normal healthy control. To assess changes induced by different treatments, levels of RA-associated inflammatory cytokines and biomarkers were measured in the serum, knee joints, and synovial tissue, using ELISA and Real Time-qPCR. Histopathological features of knee joints were analyzed for all groups. Results showed that combined MSC and IL-4 treatment alleviated signs of synovitis in CIA mice, reverting to the values of healthy controls. This was evident by the decrease in the levels of rheumatic factor (RF), C-reactive protein (CRP) and anti-nuclear antibodies (ANA) by 64, 80, and 71%, respectively, compared to the diseased group. Moreover, tumor necrosis factor-alpha (TNF- α) and monocyte chemoattractant protein-1 (MCP-1) levels decreased by 63 and 68%, respectively. Similarly, our gene expression data showed improvement in mice receiving combined therapy compared to other groups receiving single treatment, where cartilage oligomeric matrix protein (Comp), tissue inhibitor metalloproteinase-1 (Timp1), matrix metalloproteinase1 (Mmp-1), and IL-1 receptor (Il-1r) gene expression levels decreased by 75, 70, and 78%, respectively. Collectively, treatment with a combined therapy of MSC and IL-4 might have an efficient therapeutic effect on arthritis. Thus, further studies are needed to assess the potential of different MSC populations in conjugation with IL-4 in the treatment of experimental arthritis.

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Effect of estrogen receptor β agonists on proliferation and gene expression of ovarian cancer cells

BMC Cancer ◽

10.1186/s12885-017-3246-0 ◽

2017 ◽

Vol 17 (1) ◽

Cited By ~ 16

Author(s):

Susanne Schüler-Toprak ◽

Christoph Moehle ◽

Maciej Skrzypczak ◽

Olaf Ortmann ◽

Oliver Treeck

Keyword(s):

Gene Expression ◽

Ovarian Cancer ◽

Estrogen Receptor ◽

Cancer Cells ◽

Estrogen Receptor Β ◽

Ovarian Cancer Cells

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Bile acids upregulate BRCA1 and downregulate estrogen receptor 1 gene expression in ovarian cancer cells

European Journal of Cancer Prevention ◽

10.1097/cej.0000000000000398 ◽

2018 ◽

Vol 27 (6) ◽

pp. 553-556 ◽

Cited By ~ 1

Author(s):

Qunyan Jin ◽

Olivier Noel ◽

Mai Nguyen ◽

Lionel Sam ◽

Glenn S. Gerhard

Keyword(s):

Gene Expression ◽

Ovarian Cancer ◽

Estrogen Receptor ◽

Cancer Cells ◽

Bile Acids ◽

Ovarian Cancer Cells ◽

Estrogen Receptor 1

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SLC26A2 gene expression levels in melanoma

European Journal of Public Health ◽

10.1093/eurpub/ckab120.071 ◽

2021 ◽

Vol 31 (Supplement_2) ◽

Author(s):

Diana Assis ◽

Ana Luísa De Sousa-Coelho

Keyword(s):

Gene Expression ◽

Cancer Cells ◽

Normal Skin ◽

Braf Inhibitor ◽

Ovarian Cancer Cells ◽

Data Sets ◽

Dependent Manner ◽

Therapeutic Decisions ◽

Pharmacological Screening ◽

And Function

Abstract Background A recent repurposing pharmacological screening revealed that vanadium-containing drugs anti-proliferative action in ovarian cancer cells was SLC26A2-dependent. SLC26A2/DTDST is a sulfate transporter, related to chondrodysplasia syndromes. Despite some reports on colon cancer, there are no studies on SLC26A2 performed in melanoma in the literature. Methods To better understand its potential use as biomarker for therapeutic decisions in melanoma, we performed gene expression analyses of the data available at GEO profiles (NCBI). Gene data sets that allowed analysis of SLC26A2 expression (1) in melanoma; (2) in response to drugs; (3) regulated by other proteins, were selected. Results Our results showed that, compared to normal skin or benign nevi, SLC26A2 expression was 2.5-fold higher in malignant melanoma (P = 0.019). Compared to the primary tumor, SLC26A2 expression tripled in melanoma (P = 0.022). We found a 6% decrease of SLC26A2 expression in A375 melanoma cells treated with BRAF inhibitor Vemurafenib (P < 0.001). After treatment of A375 cells with MLN4924, a selective inhibitor of the activating enzyme of Nedd8, SLC26A2 decreased in a time-dependent manner ( > 80% at 24 h; P < 0.001). In Sk-Mel-2 cells overexpressing E2F-1, a transcription factor that induces apoptosis in cancer cells, SLC26A2 levels were reduced by 76.4% (P = 0.067). In A375P cells depleted of PGC1α, an important metabolic co-activator in mitochondrial biogenesis and function, SLC26A2 levels increased 16% (P = 0.013). Conclusions From this work, we unveiled, for the first time, potential clues to better understand the regulation and role of SLC26A2 in melanoma. Though, it is still to be determined whether SLC26A2 is a driver or a passenger in the disease.

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Mummy Induces Apoptosis Through Inhibiting of Epithelial-Mesenchymal Transition (EMT) in Human Breast Cancer Cells

Galen Medical Journal ◽

10.31661/gmj.v9i0.1812 ◽

2020 ◽

Vol 9 ◽

pp. 1812

Author(s):

Solmaz Rahmani Barouji ◽

Arman Shahabi ◽

Mohammadali Torbati ◽

Seyyed Mohammad Bagher Fazljou ◽

Ahmad Yari Khosroushahi

Keyword(s):

Breast Cancer ◽

Gene Expression ◽

Anticancer Activity ◽

Cancer Cells ◽

Breast Cancer Cells ◽

Epithelial Mesenchymal Transition ◽

Control Group ◽

Mrna Levels ◽

Mesenchymal Transition ◽

Mcf 7

Background: Mummy (Iranian pure shilajit) is a remedy with possessing anti-inflammatory, antioxidant and anticancer activities. This study aimed to examine mummy effects on epithelial-mesenchymal transition (EMT) and invasiveness of MCF-7 and MDA-MB-231 breast cancer (BC) cell lines with underlying its mechanism. Materials and Methods: The dose-dependent inhibitory effect of the mummy on cell proliferation in vitro was determined using the MTT assay. Flow cytometry and 4’,6-diamidino-2-phenylindole dihydrochloride staining were respectively used for quantitative and qualitative analysis of cellular apoptosis, and gene expression analysis was conducted using real-time PCR. Results: MDA-MB-231 showed more sensitivity than the MCF-7 cell line to the anticancer activity of mummy, while mummy did not exhibit significant cell cytotoxicity against human normal cells (MCF-10A). The gene expression profile demonstrated a significant decrease in TGF-β1, TGF-βR1, TWIST1, NOTCH1, CTNNB1, SRC along with an increase in E-cadherin mRNA levels in mummy treated cells compared to the untreated control group (P≤0.05). Conclusion: Mummy triggers inhibition of EMT and metastasis in breast cancer cells mainly through the downregulation of TGFβ1 activity, and more studies required to find its specific anticancer activity with details. [GMJ.2020;9:e1812]

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Anlotinib enhanced penpulimab efficacy through remodeling of tumor vascular architecture and immune microenvironment in hPD-L1/hPD-1 humanized mouse model.

Journal of Clinical Oncology ◽

10.1200/jco.2021.39.15_suppl.2581 ◽

2021 ◽

Vol 39 (15_suppl) ◽

pp. 2581-2581

Author(s):

Yunlong Shan ◽

Chongjin Zhong ◽

Qi Ni ◽

Mengying Zhang ◽

Guangji Wang ◽

...

Keyword(s):

Combination Therapy ◽

Mouse Model ◽

Immune Cells ◽

Immune Checkpoint ◽

Tumor Volume ◽

Combined Therapy ◽

Control Group ◽

Tyrosine Kinase Receptor ◽

Humanized Mouse ◽

Humanized Mouse Model

2581 Background: Even though immune checkpoint inhibitor (ICI) such as anti-PD-1 mAb has emerged as effective treatment for tumor regression, the response rate of ICI monotherapy in solid tumor is low. Many studies have demonstrated that the efficacy of combination therapy of ICI and anti-angiogenesis was superior to monotherapy. Penpulimab (AK105), a humanized IgG1 mAb that blocks PD-1 binding to PD-L1, engineered to eliminate FcγR binding and ADCC/ADCP completely. Here, we explore a new combined therapy of penpulimab and anlotinib, an oral multi-targeted tyrosine kinase receptor inhibitor. Methods: MC38-hPD-L1 tumor-bearing B-hPD-1 humanized mouse model were conducted to investigate the effects of anlotinib (1 mg/kg, every day, p.o) or penpulimab (5 mg/kg, twice a week, i.p) alone or in combination. Immunofluorescence was applied to elucidate tumor vessel normalization. In vivo imaging was conducted to detect the distribution of AF647-labelled penpulimab after anlotinib treatment. Flow cytometry and other techniques were performed to investigate intratumoral immune cells. Results: After 3-week treatment, immunotherapeutic administration of anlotinib or penpulimab showed moderate inhibition of tumor growth (tumor volume: 66.5% and 58.4% of control group, respectively), while combined treatment of anlotinib with penpulimab significantly decreased tumor volume to 36.5% of control group. Tissue pathological and blood biochemical results showed no significant toxic and side effects. Immunohistochemistry revealed that anlotinib induced tumor vascular normalization, indicated by decreased CD31+ area, increased α-SMA around tumor vessels and reduced GLUT1+ area. Furthermore, anlotinib markedly enhanced the delivery of AF647-penpulimab into tumors. Combining anlotinib with penpulimab also promoted infiltration and activity of anti-tumoral immune cells by reducing the level of immune checkpoint TIM3 and increasing the IFNγ secretion from T cells. Conclusions: Our work provides a strong scientific rationale for the combination therapy of anlotinib and penpulimab to improve tumor microenvironment and immunotherapy, which highlights the clinical potential for this new combined therapy.

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Effects of siRNA-mediated silencing of Bmi-1 gene expression on proliferation of gastric cancer cells

European Journal of Inflammation ◽

10.1177/2058739219845534 ◽

2019 ◽

Vol 17 ◽

pp. 205873921984553

Author(s):

Ying Guo ◽

Li Zhang ◽

Guangyu Zhou ◽

Qingjie Ma ◽

Shi Gao ◽

...

Keyword(s):

Gene Expression ◽

Gastric Cancer ◽

Flow Cytometry ◽

Cancer Cells ◽

Cancer Cell ◽

Gastric Cancer Cell ◽

Negative Control ◽

Control Group ◽

Gastric Cancer Cells ◽

Ags Cells

This study was designed to investigate the effects of siRNA-mediated silencing of Bmi-1 gene expression on proliferation of AGS gastric cancer cell. siRNA Bmi-1 was transfected into human AGS gastric cancer cells by liposome (as siRNA Bmi-1 group) with negative control (as control group); the expressions of Bmi-1 and apoptosis-related genes like P21, Bax, and Bcl-2 in AGS cells were determined by Western blot method; the apoptosis of AGS cells was detected by flow cytometry double staining and Hoechst staining; and cell cycle was measured by flow cytometry. Compared with the control group, the expression of Bmi-1 in the siRNA Bmi-1 group was significantly decreased ( P < 0.05), the apoptosis rate was increased ( P < 0.05), and cell cycles were arrested at G1 phase (P < 0.05); the expression level of P21 and Bax in cells was significantly up-regulated while that of Bcl-2 down-regulated ( P < 0.05). The down regulation of Bmi-1 can inhibit the proliferation of AGS gastric cancer cell and promote its apoptosis, which takes such effects mainly by up-regulating P21 as well as Bax and down-regulating Bcl-2.

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Wild-Type Tumor Repressor Protein 53 (TRP53) Promotes Ovarian Cancer Cell Survival

Endocrinology ◽

10.1210/en.2011-2131 ◽

2012 ◽

Vol 153 (4) ◽

pp. 1638-1648 ◽

Cited By ~ 19

Author(s):

Lisa K. Mullany ◽

Zhilin Liu ◽

Erin R. King ◽

Kwong-Kwok Wong ◽

JoAnne S. Richards

Keyword(s):

Gene Expression ◽

Cell Cycle ◽

Ovarian Cancer ◽

Dna Repair ◽

Cell Survival ◽

Cancer Cells ◽

Ovarian Cancer Cells ◽

Low Grade ◽

Wild Type ◽

Repressor Protein

Loss of Pten in the KrasG12D;Amhr2-Cre mutant mice leads to the transformation of ovarian surface epithelial (OSE) cells and rapid development of low-grade, invasive serous adenocarcinomas. Tumors occur with 100% penetrance and express elevated levels of wild-type tumor repressor protein 53 (TRP53). To test the functions of TRP53 in the Pten;Kras (Trp53+) mice, we disrupted the Trp53 gene yielding Pten;Kras(Trp53−) mice. By comparing morphology and gene expression profiles in the Trp53+ and Trp53− OSE cells from these mice, we document that wild-type TRP53 acts as a major promoter of OSE cell survival and differentiation: cells lacking Trp53 are transformed yet are less adherent, migratory, and invasive and exhibit a gene expression profile more like normal OSE cells. These results provide a new paradigm: wild-type TRP53 does not preferentially induce apoptotic or senescent related genes in the Pten;Kras(Trp53+) cancer cells but rather increases genes regulating DNA repair, cell cycle progression, and proliferation and decreases putative tumor suppressor genes. However, if TRP53 activity is forced higher by exposure to nutlin-3a (a mouse double minute-2 antagonist), TRP53 suppresses DNA repair genes and induces the expression of genes that control cell cycle arrest and apoptosis. Thus, in the Pten;Kras(Trp53+) mutant mouse OSE cells and likely in human TP53+ low-grade ovarian cancer cells, wild-type TRP53 controls global molecular changes that are dependent on its activation status. These results suggest that activation of TP53 may provide a promising new therapy for managing low-grade ovarian cancer and other cancers in humans in which wild-type TP53 is expressed.

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