scholarly journals Enhancement of tumor tropism of mPEGylated nanoparticles by anti-mPEG bispecific antibody for ovarian cancer therapy

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Wen-Wei Lin ◽  
Yi-An Cheng ◽  
Chia-Ching Li ◽  
Kai-Wen Ho ◽  
Huei-Jen Chen ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Cancer Cells ◽  
Therapeutic Efficacy ◽  
Bispecific Antibody ◽  
Drug Susceptibility ◽  
Good Prognosis ◽  
Ovarian Cancer Cells ◽  
Tumor Tropism ◽  
Her2 Antigen ◽  
Anti Tumor Activity

AbstractOvarian cancer is highly metastatic, with a high frequency of relapse, and is the most fatal gynecologic malignancy in women worldwide. It is important to elevate the drug susceptibility and cytotoxicity of ovarian cancer cells, thereby eliminating resident cancer cells for more effective therapeutic efficacy. Here, we developed a bispecific antibody (BsAb; mPEG × HER2) that can easily provide HER2+ tumor tropism to mPEGylated liposomal doxorubicin (PLD) and further increase the drug accumulation in cancer cells via receptor-mediated endocytosis, and improve the cytotoxicity and therapeutic efficacy of HER2+ ovarian tumors. The mPEG × HER2 can simultaneously bind to mPEG molecules on the surface of PLD and HER2 antigen on the surface of ovarian cancer cells. Simply mixing the mPEG × HER2 with PLD was able to confer HER2 specificity of PLD to HER2+ ovarian cancer cells and efficiently trigger endocytosis and enhance cytotoxicity by 5.4-fold as compared to non-targeted PLD. mPEG × HER2-modified PLD was able to significantly increase the targeting and accumulation of HER2+ ovarian tumor by 220% as compared with non-targeted PLD. It could also significantly improve the anti-tumor activity of PLD (P < 0.05) with minimal obvious toxicity in a tumor-bearing mouse model. We believe that the mPEG × HER2 can significantly improve the therapeutic efficacy, potentially reduce the relapse freqency and thereby achieve good prognosis in ovarian cancer patients.

Improved therapeutic efficacy of mammalian expressed-recombinant interferon gamma against ovarian cancer cells

2017 ◽  
Vol 359 (1) ◽  
pp. 20-29 ◽  
Author(s):  
Ali Razaghi ◽  
Carina Villacrés ◽  
Vincent Jung ◽  
Narges Mashkour ◽  
Michael Butler ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Cancer Cells ◽  
Interferon Gamma ◽  
Therapeutic Efficacy ◽  
Ovarian Cancer Cells ◽  
Recombinant Interferon

scholarly journals 3D Clinorotation Affects Drug Sensitivity of Human Ovarian Cancer Cells

2021 ◽  
Vol 33 (3) ◽  
Author(s):  
Dawid Przystupski ◽  
Agata Górska ◽  
Anna Szewczyk ◽  
Małgorzata Drąg-Zalesińska ◽  
Julita Kulbacka
Keyword(s):  
Cell Cycle ◽  
Ovarian Cancer ◽  
Cancer Cells ◽  
Cancer Biology ◽  
Drug Susceptibility ◽  
Ovarian Cancer Cells ◽  
Human Ovarian Cancer ◽  
Altered Gravity ◽  
Cellular Mechanisms ◽  
Short Term Exposure

AbstractNumerous studies have reported that gravity alteration displays a remarkable influence on the biological processes of cancer cells. Therefore, gravity-related experiments have become a promising method of improving knowledge in the field of cancer biology and may be useful to detect remarkable implications for future cancer treatment. Taking this concept further, we used a 3D clinostat (3D-C; 10 rpm of changing direction) to analyse the effect of short-term exposure to simulated microgravity (sμg) on cisplatin sensitivity of drug resistant human ovarian cancer cells SKOV-3. This allowed us to investigate whether altered gravity affects drug susceptibility of cancer cells. Our studies revealed that sμg exposure affects SKOV-3 cells morphology and drug efficiency. We observed the altered cell shape, the presence of membrane blebbing and lamellipodia as well as the lack of filopodia when the cells had been cultured on 3D-C for 2 h. Cytotoxicity, cell death and cell cycle assays showed an increased percentage of apoptotic cells and G0/G1 cell cycle arrest after exposure on the 3D-C with cisplatin in comparison to the static control, non clinorotated cells. Cell proliferation and migration were altered after the exposure to sμg as well. Our studies suggest that the altered gravity conditions affected cellular mechanisms involved in cisplatin resistance, resulting in higher sensitivity of cancer cells to the chemotherapeutic. The investigation and clarification of these results may be a crucial step toward improving our understanding of the relationship between cellular resistance to chemotherapy and the response to altered gravitational conditions.

scholarly journals Tankyrase Promotes Aerobic Glycolysis and Proliferation of Ovarian Cancer through Activation of Wnt/β-Catenin Signaling

2019 ◽  
Vol 2019 ◽  
pp. 1-14 ◽  
Author(s):  
Hong-Yi Yang ◽  
Jin-Xing Shen ◽  
Yi Wang ◽  
Yu Liu ◽  
Dong-Yan Shen ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Cancer Cells ◽  
Molecular Mechanisms ◽  
Lung Tumor ◽  
Aerobic Glycolysis ◽  
Hepatocellular Cancer ◽  
Drug Susceptibility ◽  
Ovarian Cancer Cells ◽  
Human Lung Tumor ◽  
Consumption Rates

Tankyrase (TNKS) plays important roles in the malignancy of several cancers such as human lung tumor, breast cancer, and hepatocellular cancer. However, its exact functions and molecular mechanisms in ovarian cancer remain unclear. In this study, we found that TNKS was aberrantly overexpressed in human ovarian cancer tissues and associated with poor patient prognosis. TNKS inhibition or knockdown not only reduced ovarian cancer cell proliferation, colony formation, migration, invasion, and tumorigenic potential in nude mice but also enhanced the drug susceptibility of ovarian cancer cells through arresting cell cycle and inducing apoptosis. These phenotypic changes correlated with downregulation of targets (Cyclin D1, MDR, and MMP-9) of Wnt/β-catenin signaling. Furthermore, downregulation of TNKS suppressed the glucose uptake, lactate excretion, and cellular ATP levels and increased cellular O2consumption rates. Molecular mechanism studies revealed that TNKS promoted aerobic glycolysis at least in part due to upregulation of pyruvate carboxylase (PC) via activation of Wnt/β-catenin/snail signaling. In agreement with these findings, expression of TNKS is positively associated with snail and PC in clinical ovarian cancer samples. Our findings identified TNKS as an oncogenic regulator of ovarian cancer cells proliferation that promotes aerobic glycolysis via activation of Wnt/β-catenin signaling, indicating that the TNKS might serve as a potential molecular target for clinical therapy of Wnt/β-catenin dependent ovarian cancer.

scholarly journals Ovarian cancer cells with CD133+ phenotype is more resistant against Ngai Bun Boesenbergia pandurata extract than original ovarian cancer cells

2020 ◽  
Vol 7 (1) ◽  
pp. 290-295
Author(s):  
Oanh Thi-Kieu Nguyen ◽  
Phuc Van Pham
Keyword(s):  
Ovarian Cancer ◽  
Traditional Medicine ◽  
Cancer Cells ◽  
Chloroform Extract ◽  
Research Field ◽  
Ovarian Cancer Cells ◽  
Root Extract ◽  
Tropical Plants ◽  
Ic50 Values ◽  
Anti Tumor Activity

Introduction: Ovarian cancer is one of the most common cancers in women. Due to the difficulty in early detection and treatment of ovarian cancer, many research studies and clinical trials have been developed to discover more efficient therapies. Besides Western medicine, traditional medicine has gained increased interest as a research field with potential to lead to the production of marketable therapeutic products. With the diversity of tropical plants in Asia, traditional medicine has been very popular and has served as a traditional therapy for generations. The Ngai bun (Boesenbergia pandurata) root is used not only as a food spice but also in ethnomedicine. This study aimed to compare the anti-tumor activity of Boesenbergia pandurata root extract against ovarian cancer cells and CD133+ ovarian cancer cells that were enriched from the original ovarian cancer cells. Methods: Crude extract of Boesenbergia pandurata roots were prepared in two kinds of solvents (methanol and chloroform). The ovarian cancer cells OVP-10 were used in this study. The population of CD133+ ovarian cancer cells (CD133+OVP-10) were sorted from the OVP-10 cancer cells. Both OVP-10 cells and CD133+OVP-10 cells were treated with these crude extracts. Adiposederived stem cells (ADSCs) were used as control normal cells for all assays. The anti-tumor activity of extracts were evaluated based on the IC50 values. Results: Based on the IC50 index, the chloroform extract had an anti-tumor activity higher than that of methanol extract, on both OVP-10 and CD133+OPV-10 cells (IC50 of methanol and chloroform extracts were 330.1 +/- 16.9 ug/mL and 246.5 +/- 21.2 ug/mL, respectively, for OVP-10 cells; IC50 of methanol and chloroform extracts were 411.8 +/- 83.7 ug/mL and 307 +/- 9.2 ug/mL respectively, for CD133+OVP-10 cells). The results also showed that CD133+OVP-10 cells were more resistant to chloroform extract than were OVP-10 cells (307 +/- 9.2 mg/mL vs. 246.5 +/- 21.2 mg/mL, respectively, for CD133+OVP-10 vs. OVP-10 cells, p < 0.05). Conclusion: The chloroform extract of Boesenbergia pandurata roots displayed strong antitumor activity against ovarian cancer cells OVP-10 and CD133+OVP-10; the latter cells were found to be more resistant than the original ovarian cancer cells.  

Cytotoxic effects of disulfiram and synergism with cisplatin on ovarian cancer cells in vitro

2018 ◽  
Author(s):  
F Guo ◽  
Z Yang ◽  
J Xu ◽  
J Sehouli ◽  
AE Albers ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Cancer Cells ◽  
Ovarian Cancer Cells ◽  
Cytotoxic Effects
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