Rembiałkowska Nina, Baczyńska Dagmara, Dubińska-Magiera Magda, Choromańska Anna, Bieżuńska-Kusiak Katarzyna, Gajewska-Naryniecka Agnieszka, Novickij Vitalij, Saczko Jolanta, Przystupski Dawid, Kulbacka Julita
Department of Molecular and Cellular Biology, Faculty of Pharmacy, Wroclaw Medical University, Borowska 211A, 50-556 Wroclaw, Poland.
Department of Animal Developmental Biology, Faculty of Biological Science, University of Wroclaw, Sienkiewicza 21, 50-335 Wroclaw, Poland.
Membranes (Basel). 2022 Apr 21;12(5):448. doi: 10.3390/membranes12050448.
(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.
(1) 背景：本研究的主要目的是确定重力改变是否会改变细胞活力、改善药物递送并调节耐药相关基因的表达。(2) 方法：本研究调查了微重力在人耐药和敏感胃癌细胞（EPG85 - 257 RDB）和（EPG85 - 257 P）中激活的细胞内机制。我们使用美国国家航空航天局开发的旋转细胞培养系统（RCCS）使细胞暴露于改变的重力环境中。通过RCCS生物反应器模拟微重力的抗肿瘤潜力，并在敏感细胞系中与化疗耐药细胞相比评估其对药物敏感癌细胞的有效性。通过活力测定、细胞骨架成像、多药耐药（MDR）基因表达分析、线粒体编码细胞色素C氧化酶I（MTCO - 1）和8 - 羟基脱氧鸟苷免疫细胞化学分析来评估微重力与化疗联合的效果。(3) 结果：我们发现改变的重力与阿霉素联合对癌细胞具有细胞毒性。模拟微重力处理后的细胞显示耐药相关基因表达降低，DNA/RNA损伤标志物表达增加。细胞骨架评估表明，暴露于改变的重力条件后，F - 肌动蛋白纤维发生了显著重组。(4) 结论：模拟微重力引起的细胞内改变可增加胃癌细胞对化疗的敏感性。我们获得了令人满意的结果，显示了重力改变与MDR现象之间的相关性，这在未来的治疗应用中似乎很有前景。
