RCCS Bioreactor-Based Modeled Microgravity Affects Gastric Cancer Cells and Improves the Chemotherapeutic Effect

Membranes

Magda Dubińska-Magiera¹  Jolanta Saczko²  Anna Choromańska²  Agnieszka Gajewska-Naryniecka²  Katarzyna Bieżuńska-Kusiak²  Dagmara Baczyńska²  Nina Rembiałkowska²  Julita Kulbacka²  Dawid Przystupski³  Vitalij Novickij⁴ 

[1] Department of Animal Developmental Biology, Faculty of Biological Science, University of Wroclaw, Sienkiewicza 21, 50-335 Wroclaw, Poland;Department of Molecular and Cellular Biology, Faculty of Pharmacy, Wroclaw Medical University, Borowska 211A, 50-556 Wroclaw, Poland;Department of Pediatric Bone Marrow Transplantation, Oncology and Hematology, Wroclaw Medical University, Borowska 213, 50-556 Wroclaw, Poland;Institute of High Magnetic Fields, Vilnius Gediminas Technical University, 03227 Vilnius, Lithuania;

关键词: microgravity;    drug resistance;    gastric cancer;    doxorubicin;    cytoskeleton;   

DOI  :  10.3390/membranes12050448

来源: DOAJ

【 摘 要 】

(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.

【 授权许可】

Unknown