Sensitivity of EGFR/HER-2 Positive Cells Isolated from Ascitic Fluid of Advanced Ovarian Cancer Patients to EGFR/HER-2 Inhibitors
| Autor: | Dianne Harker, Bryony Simcock, Peter Sykes, Kenny Chitcholtan |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
EGFR Population Cell gefitinib lcsh:Technology lcsh:Chemistry 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Gefitinib medicine Adjuvant therapy General Materials Science education lcsh:QH301-705.5 Instrumentation Protein kinase B canertinib Fluid Flow and Transfer Processes education.field_of_study cell clusters Canertinib lcsh:T business.industry ascitic fluid Process Chemistry and Technology General Engineering medicine.disease lcsh:QC1-999 Computer Science Applications 030104 developmental biology medicine.anatomical_structure ovarian cancer lcsh:Biology (General) lcsh:QD1-999 chemistry lcsh:TA1-2040 HER-2 030220 oncology & carcinogenesis Cancer cell Cancer research lcsh:Engineering (General). Civil engineering (General) Ovarian cancer business lcsh:Physics medicine.drug |
| Zdroj: | Applied Sciences Volume 10 Issue 7 Applied Sciences, Vol 10, Iss 2343, p 2343 (2020) |
| ISSN: | 2076-3417 |
| DOI: | 10.3390/app10072343 |
| Popis: | Background: advanced ovarian cancer often presents with ascites. These ascites contain small clusters of cancer cells, which may contribute greatly to the metastatic potential of ovarian cancer in the peritoneal cavity. Therefore, understanding the unique protein expressions of this cell population will provide vital information for the development of tailored, targeted treatment. In this study, we isolate floating ovarian cancer cells from ovarian cancer patient ascitic fluid and use these cells to document that the expression of EGFR/HER-2 proteins may be essential for the growth and survival of these floating cancer cell clusters. Methods: ascitic fluid-derived cells were isolated from ascitic fluid by using Ficoll separation. Cells were cultured in a non-adherent condition for six days. The protein level of EGFR, HER-2, AKT, and ERK and their phosphorylation in ovarian cancer cell lines were determined by immunofluorescence. The immunofluorescent staining for proteins presented in ascitic fluid-derived cells determined the intensity profile of each protein using Carl Zeiss Blue software. Results: Isolated ovarian cancer cells from ascitic fluid have a measurable level of EGFR and HER-2 proteins. The inhibition of EGFR and EGFR/HER-2 positive cells with gefitinib and canertinib selectively disrupts cell viability and the protein level of EGFR, HER-2, AKT and ERK and their respective phosphorylation status. In addition, the dual EGFR/HER-2 inhibitor canertinib demonstrates greater anti-tumour effects than gefitinib in EGFR/HER-2 positive cells. Conclusion: These studies reveal an important role of multiple activation of receptor tyrosine kinases in floating ovarian cancer cells, as well as the importance of a dual EGFR/HER-2 inhibitor used as alternative adjuvant therapy in advanced ovarian cancer patients. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|