RCCS Bioreactor-Based Modeled Microgravity Affects Gastric Cancer Cells and Improves the Chemotherapeutic Effect
(1) Background: The main purpose of the study was to determine whether altered gravity might alter cell viability, improve drug delivery and modulate the expression of drug resistance-related genes. (2) Methods: This study investigated the intracellular mechanisms activated by microgravity in human...
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MDPI AG
2022-04-01
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Series: | Membranes |
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Online Access: | https://www.mdpi.com/2077-0375/12/5/448 |
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author | Nina Rembiałkowska Dagmara Baczyńska Magda Dubińska-Magiera Anna Choromańska Katarzyna Bieżuńska-Kusiak Agnieszka Gajewska-Naryniecka Vitalij Novickij Jolanta Saczko Dawid Przystupski Julita Kulbacka |
author_facet | Nina Rembiałkowska Dagmara Baczyńska Magda Dubińska-Magiera Anna Choromańska Katarzyna Bieżuńska-Kusiak Agnieszka Gajewska-Naryniecka Vitalij Novickij Jolanta Saczko Dawid Przystupski Julita Kulbacka |
author_sort | Nina Rembiałkowska |
collection | DOAJ |
description | (1) Background: The main purpose of the study was to determine whether altered gravity might alter cell viability, improve drug delivery and modulate the expression of drug resistance-related genes. (2) Methods: This study investigated the intracellular mechanisms activated by microgravity in human resistant and sensitive gastric cancer cells (EPG85-257 RDB) and (EPG85-257 P). We used a rotary cell culture system (RCCS) developed by NASA to expose cells to altered gravity. The antitumor potential of microgravity was simulated by the RCCS bioreactor, and its effectiveness was evaluated in sensitive cell lines compared to chemotherapy-resistant cells concerning drug-sensitive cancer cells. Microgravity with chemotherapy was estimated by the viability assay, cytoskeleton imaging, MDR (multidrug resistance) gene expression analysis, MTCO-1 (mitochondrially encoded cytochrome C oxidase I), and 8-OHdG immunocytochemical analysis. (3) Results: We found that altered gravity combined with doxorubicin was cytotoxic to cancer cells. Cells following simulated microgravity revealed decreased expression of genes related to drug resistance and increased DNA/RNA damage marker expression. Cytoskeleton evaluation demonstrated significant reorganization of F-actin fibers after exposure to changed gravity conditions. (4) Conclusions: Intracellular alterations caused by simulated microgravity can increase gastric cancer cells’ sensitivity to chemotherapy. We have obtained satisfactory results showing the correlation between altered gravity and MDR phenomena which seems promising in future therapeutic applications. |
first_indexed | 2024-03-10T03:27:22Z |
format | Article |
id | doaj.art-cdb0d4f6280246fd8998340a30936eab |
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issn | 2077-0375 |
language | English |
last_indexed | 2024-03-10T03:27:22Z |
publishDate | 2022-04-01 |
publisher | MDPI AG |
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series | Membranes |
spelling | doaj.art-cdb0d4f6280246fd8998340a30936eab2023-11-23T12:04:52ZengMDPI AGMembranes2077-03752022-04-0112544810.3390/membranes12050448RCCS Bioreactor-Based Modeled Microgravity Affects Gastric Cancer Cells and Improves the Chemotherapeutic EffectNina Rembiałkowska0Dagmara Baczyńska1Magda Dubińska-Magiera2Anna Choromańska3Katarzyna Bieżuńska-Kusiak4Agnieszka Gajewska-Naryniecka5Vitalij Novickij6Jolanta Saczko7Dawid Przystupski8Julita Kulbacka9Department of Molecular and Cellular Biology, Faculty of Pharmacy, Wroclaw Medical University, Borowska 211A, 50-556 Wroclaw, PolandDepartment of Molecular and Cellular Biology, Faculty of Pharmacy, Wroclaw Medical University, Borowska 211A, 50-556 Wroclaw, PolandDepartment of Animal Developmental Biology, Faculty of Biological Science, University of Wroclaw, Sienkiewicza 21, 50-335 Wroclaw, PolandDepartment of Molecular and Cellular Biology, Faculty of Pharmacy, Wroclaw Medical University, Borowska 211A, 50-556 Wroclaw, PolandDepartment of Molecular and Cellular Biology, Faculty of Pharmacy, Wroclaw Medical University, Borowska 211A, 50-556 Wroclaw, PolandDepartment of Molecular and Cellular Biology, Faculty of Pharmacy, Wroclaw Medical University, Borowska 211A, 50-556 Wroclaw, PolandInstitute of High Magnetic Fields, Vilnius Gediminas Technical University, 03227 Vilnius, LithuaniaDepartment of Molecular and Cellular Biology, Faculty of Pharmacy, Wroclaw Medical University, Borowska 211A, 50-556 Wroclaw, PolandDepartment of Pediatric Bone Marrow Transplantation, Oncology and Hematology, Wroclaw Medical University, Borowska 213, 50-556 Wroclaw, PolandDepartment of Molecular and Cellular Biology, Faculty of Pharmacy, Wroclaw Medical University, Borowska 211A, 50-556 Wroclaw, Poland(1) Background: The main purpose of the study was to determine whether altered gravity might alter cell viability, improve drug delivery and modulate the expression of drug resistance-related genes. (2) Methods: This study investigated the intracellular mechanisms activated by microgravity in human resistant and sensitive gastric cancer cells (EPG85-257 RDB) and (EPG85-257 P). We used a rotary cell culture system (RCCS) developed by NASA to expose cells to altered gravity. The antitumor potential of microgravity was simulated by the RCCS bioreactor, and its effectiveness was evaluated in sensitive cell lines compared to chemotherapy-resistant cells concerning drug-sensitive cancer cells. Microgravity with chemotherapy was estimated by the viability assay, cytoskeleton imaging, MDR (multidrug resistance) gene expression analysis, MTCO-1 (mitochondrially encoded cytochrome C oxidase I), and 8-OHdG immunocytochemical analysis. (3) Results: We found that altered gravity combined with doxorubicin was cytotoxic to cancer cells. Cells following simulated microgravity revealed decreased expression of genes related to drug resistance and increased DNA/RNA damage marker expression. Cytoskeleton evaluation demonstrated significant reorganization of F-actin fibers after exposure to changed gravity conditions. (4) Conclusions: Intracellular alterations caused by simulated microgravity can increase gastric cancer cells’ sensitivity to chemotherapy. We have obtained satisfactory results showing the correlation between altered gravity and MDR phenomena which seems promising in future therapeutic applications.https://www.mdpi.com/2077-0375/12/5/448microgravitydrug resistancegastric cancerdoxorubicincytoskeleton |
spellingShingle | Nina Rembiałkowska Dagmara Baczyńska Magda Dubińska-Magiera Anna Choromańska Katarzyna Bieżuńska-Kusiak Agnieszka Gajewska-Naryniecka Vitalij Novickij Jolanta Saczko Dawid Przystupski Julita Kulbacka RCCS Bioreactor-Based Modeled Microgravity Affects Gastric Cancer Cells and Improves the Chemotherapeutic Effect Membranes microgravity drug resistance gastric cancer doxorubicin cytoskeleton |
title | RCCS Bioreactor-Based Modeled Microgravity Affects Gastric Cancer Cells and Improves the Chemotherapeutic Effect |
title_full | RCCS Bioreactor-Based Modeled Microgravity Affects Gastric Cancer Cells and Improves the Chemotherapeutic Effect |
title_fullStr | RCCS Bioreactor-Based Modeled Microgravity Affects Gastric Cancer Cells and Improves the Chemotherapeutic Effect |
title_full_unstemmed | RCCS Bioreactor-Based Modeled Microgravity Affects Gastric Cancer Cells and Improves the Chemotherapeutic Effect |
title_short | RCCS Bioreactor-Based Modeled Microgravity Affects Gastric Cancer Cells and Improves the Chemotherapeutic Effect |
title_sort | rccs bioreactor based modeled microgravity affects gastric cancer cells and improves the chemotherapeutic effect |
topic | microgravity drug resistance gastric cancer doxorubicin cytoskeleton |
url | https://www.mdpi.com/2077-0375/12/5/448 |
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