Short and long time effects of low temperature Plasma Activated Media on 3D multicellular tumor spheroids.
Short and long time effects of low temperature Plasma Activated Media on 3D multicellular tumor spheroids.
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DOI：
10.1038/srep21421
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发表时间：
2016-02-22
影响因子：
4.6
通讯作者：
Merbahi N
中科院分区：
文献类型：
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作者：
Judée F;Fongia C;Ducommun B;Yousfi M;Lobjois V;Merbahi N
这项工作研究了血浆激活介质（PAM）对结肠腺癌多细胞肿瘤球体（MCTS）的区域化抗增殖作用，MCTS是一种模拟微肿瘤区域的3D组织和区域化的模型。利用介质阻挡等离子体射流装置与氦气载气交叉产生PAM。MCTS在血浆暴露后的不同时间转移到PAM中长达48小时，并评价对MCTS生长和DNA损伤的影响。我们报告了血浆暴露时间和转移前延迟对MCTS生长和DNA损伤的影响。在最外层观察到由组蛋白H2 AX磷酸化揭示的DNA损伤的局部积累，并且依赖于血浆暴露。通过添加过氧化氢酶完全恢复DNA损伤，表明H2 O2在观察到的遗传毒性效应中起主要作用，同时保持生长抑制效应，表明这是由于其他反应性物质。SOD和D-甘露醇清除剂也减少了30%的DNA损伤，表明和OH* 参与H2 O2的形成。最后，PAM在+4 °C或−80 °C下储存时能够保持其细胞毒性和遗传毒性活性。这些结果表明，血浆激活培养基可能是一个有前途的新的抗结直肠癌肿瘤的策略。
This work investigates the regionalized antiproliferative effects of plasma-activated medium (PAM) on colon adenocarcinoma multicellular tumor spheroid (MCTS), a model that mimics 3D organization and regionalization of a microtumor region. PAM was generated by dielectric barrier plasma jet setup crossed by helium carrier gas. MCTS were transferred in PAM at various times after plasma exposure up to 48 hours and effect on MCTS growth and DNA damage were evaluated. We report the impact of plasma exposure duration and delay before transfer on MCTS growth and DNA damage. Local accumulation of DNA damage revealed by histone H2AX phosphorylation is observed on outermost layers and is dependent on plasma exposure. DNA damage is completely reverted by catalase addition indicating that H2O2 plays major role in observed genotoxic effect while growth inhibitory effect is maintained suggesting that it is due to others reactive species. SOD and D-mannitol scavengers also reduced DNA damage by 30% indicating that and OH* are involved in H2O2 formation. Finally, PAM is able to retain its cytotoxic and genotoxic activity upon storage at +4 °C or −80 °C. These results suggest that plasma activated media may be a promising new antitumor strategy for colorectal cancer tumors.