Effects of trastuzumab on the proliferation and apoptosis of ovarian cancer cells

Cong, Jianglin; Liu, R; Hou, Jianquan; Wang, X; Jiang, Haiyang; Wang, J

doi:10.4149/neo_2018_180724n524

Cited by 3 publications

(2 citation statements)

References 19 publications

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“…HER2 is found in the cytoplasm of normal cells, mainly in the mitochondrial cristae, with little amounts occurring on the cell membrane; HER2 is found only on the cell membrane in tumor cells. The expression of HER2 in normal ovarian epithelium is very low; however, the expression in epithelial ovarian tumor tissue has been reported to be high at 55 times that of normal ovarian epithelium ( 126 ). Epithelial ovarian cancer consists of histological subtypes, which include serous carcinoma (prevalence 75%), mucinous carcinoma (20%), endometrioid carcinoma (2%), and clear cell carcinoma (<1%).…”

Section: Discussionmentioning

confidence: 99%

Advances in the Application of Radionuclide-Labeled HER2 Affibody for the Diagnosis and Treatment of Ovarian Cancer

et al. 2022

Front. Oncol.

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Human epidermal growth factor receptor 2 (HER2) is a highly expressed tumor marker in epithelial ovarian cancer, and its overexpression is considered to be a potential factor of poor prognosis. Therefore, monitoring the expression of HER2 receptor in tumor tissue provides favorable conditions for accurate localization, diagnosis, targeted therapy, and prognosis evaluation of cancer foci. Affibody has the advantages of high affinity, small molecular weight, and stable biochemical properties. The molecular probes of radionuclide-labeled HER2 affibody have recently shown broad application prospects in the diagnosis and treatment of ovarian cancer; the aim is to introduce radionuclides into the cancer foci, display systemic lesions, and kill tumor cells through the radioactivity of the radionuclides. This process seamlessly integrates the diagnosis and treatment of ovarian cancer. Current research and development of new molecular probes of radionuclide-labeled HER2 affibody should focus on overcoming the deficiencies of non-specific uptake in the kidney, bone marrow, liver, and gastrointestinal tract, and on reducing the background of the image to improve image quality. By modifying the amino acid sequence; changing the hydrophilicity, surface charge, and lipid solubility of the affibody molecule; and using different radionuclides, chelating agents, and labeling conditions to optimize the labeling method of molecular probes, the specific uptake of molecular probes at tumor sites will be improved, while reducing radioactive retention in non-target organs and obtaining the best target/non-target value. These measures will enable the clinical use of radionuclide-labeled HER2 affibody molecular probes as soon as possible, providing a new clinical path for tumor-specific diagnosis, targeted therapy, and efficacy evaluation. The purpose of this review is to describe the application of radionuclide-labeled HER2 affibody in the imaging and treatment of ovarian cancer, including its potential clinical value and dilemmas.

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Section: Discussionmentioning

confidence: 99%

Advances in the Application of Radionuclide-Labeled HER2 Affibody for the Diagnosis and Treatment of Ovarian Cancer

et al. 2022

Front. Oncol.

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“…Aberrant protein expression and mutations in the ERBB2 gene are found in several solid tumors, including breast cancer (Ahn et al, 2020). Several approaches have been developed to target HER2 (Cong et al, 2019). The monoclonal antibody (mAb) Trastuzumab was the first anti-HER2 agent approved in combination with conventional chemotherapy for patients with HER2-positive metastatic breast cancer and subsequently approved as adjuvant therapy in patients with early-stage disease (Boekhout et al, 2011).…”

Section: Introductionmentioning

confidence: 99%

CD81-guided heterologous EVs present heterogeneous interactions with breast cancer cells

Gurrieri,

Carradori,

Roccuzzo

et al. 2024

Preprint

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Extracellular vesicles (EVs) are cell-secreted particles conceived as natural vehicles for intercellular communication. The intrinsic biocompatibility, stability in biofluids, and heterogeneous molecular cargo of EVs promise advancements in targeted therapy applications. However, predicting cell-targeting spectrum and cargo delivery are fundamental challenges for exploiting EVs or hybrid formulations. In this work, we combined cell-based and biochemical approaches to understand if secreted EVs show predictable EV-cell interactions and consequent cargo delivery. We exploited the tetraspanin CD81 to encode full-length recombinant proteins with a C-terminal GFP reporter encompassing or not Trastuzumab light chains targeting the HER2 receptor. These fusion proteins participated in vesicular trafficking dynamics and accumulated on secreted EVs when transiently over-expressed in HEK293T cells. Despite the presence of GFP, secreted EV populations retained a HER2 receptor-binding capacity and were used in EV-cell interaction assays. In time-frames where the global GFP spot distribution did not change between HER2-positive (SK-BR-3) or –negative (MDA-MB-231) breast cancer cell lines, the HER2 manipulation in isogenic cells remarkably affected the tropism of heterologous EVs. In this line, secreted doxorubicin-EVs, which showed improved efficacy compared to the free drug, had a reduced cell-killing activity on SK-BR-3 with a knocked-out HER2 receptor. Interestingly, the fusion protein-corresponding transcripts also present as full-length mRNAs in recombinant EVs could reach orthotopic breast tumors in JIMT-1-xenografted mice, as detected by ddPCR in tissue biopsies, improving our sensitivity in detecting bioavailable cargoes. These data show multiple mechanisms underlying EV-cell interactions and prioritize the profiling of surfaceomes for better comprehension of cell engagement and design new generations of EV-based nanovehicles.

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Acetogenin Extracted from Annona muricata Prevented the Actions of EGF in PA-1 Ovarian Cancer Cells

Periyasamy

Bharathi

Deivasigamani

et al. 2021

PPL

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Background: In individuals with ovarian cancer, an increase in the circulating level of the epidermal growth factor (EGF) is readily apparent. Ovarian cancer cells exhibit signaling pathway of the epidermal growth factor (EGFR) and respond to the EGF. Annona Muricata (AM) has been shown to decrease ovarian cell proliferation however, role of AM in regulating EGF actions is not yet to be reported. Objective: In this study, we proposed that the fractionated compound acetogenin can inhibit the activation of EGFRregulated signaling cascades such as MAPK7 / PI3K-Akt / mTOR / STAT upon EGF stimulation. Methods: Ethanolic extract was prepared for the whole AM plant and Thin Layer Chromatography (TLC) was performed to characterize the secondary metabolites and each fraction was assessed using kedde reagent for the presence of acetogenin. The effects of acetogenins were then tested on the survival of PA-1 ovarian cancer cells under basal and EGF stimulated conditions. To delineate the role of acetogenin in EGFR signaling cascades, the in silico docking studies were conducted. Discussion: The vital regulatory role of acetogenin reported in this study indicate significant anticancer activities of acetogenin from AM. The in silico study of the acetogenin function predicted that it binds specifically to Asp837 (phosphoracceptor site) of EGFR, essential for phosphorylation of substrates in the TK domain and RU which promote downstream signaling. Conclusion: This study, proposed that acetogenin isolated from AM effectively inhibited the survival of PA-1 ovarian cancer cells through impaired EGF signaling.

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Effects of trastuzumab on the proliferation and apoptosis of ovarian cancer cells

Cited by 3 publications

References 19 publications

Advances in the Application of Radionuclide-Labeled HER2 Affibody for the Diagnosis and Treatment of Ovarian Cancer

Advances in the Application of Radionuclide-Labeled HER2 Affibody for the Diagnosis and Treatment of Ovarian Cancer

CD81-guided heterologous EVs present heterogeneous interactions with breast cancer cells

Acetogenin Extracted from Annona muricata Prevented the Actions of EGF in PA-1 Ovarian Cancer Cells

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