School of Life Science, University of Science and Technology of China, Hefei, Anhui, 230027, China.
The CAS Key Laboratory of Innate Immunity and Chronic Disease, School of Life Sciences, University of Science and Technology of China, Hefei, Anhui, 230027, China.
Sci Rep. 2017 Aug 11;7(1):7980. doi: 10.1038/s41598-017-08792-3.
Non-thermal atmospheric plasma (NTP) has shown its selective anticancer effects in many types of tumors in vitro and one of the main mechanisms is that the different increase of intracellular ROS in cancer and homologous normal cells. In this study, we report that NTP treatment reduces the proliferation in triple negative breast cancer (TNBC) and normal cell lines. Simultaneously, STAT3 pathway is inhibited by NTP effects. However, it is observed that normal cells MCF10A are more sensitive to ROS toxicity induced by NTP than cancer cells MDA-MB-231. When 5 mM of ROS inhibitor N-acetyl cysteine (NAC) is employed in NTP treatments, the proliferation of normal breast cells MCF10A recovers. Meanwhile, NTP effects remain significant inhibition of MDA-MB-231 cells. Our results further reveal that NTP can induce apoptosis in MDA-MB-231 cells through inhibiting interleukin-6 receptor (IL-6R) pathway. Moreover, the mechanism of NTP anti-cancer selectivity relates to constantly HER2/Akt activation induced by NTP especially in MCF10A cells but not in MDA-MB-231 cells. Therefore, these two different cell signaling pathways induced by NTP treatments in TNBC and homologous normal cells make NTP becoming a potential tool in future therapy.
非热大气压等离子体(NTP)已在体外多种类型的肿瘤中显示出其选择性抗癌作用,其主要机制之一是不同的肿瘤和同源正常细胞内 ROS 水平的不同增加。在这项研究中,我们报告 NTP 处理可降低三阴性乳腺癌(TNBC)和正常细胞系的增殖。同时,NTP 作用抑制了 STAT3 通路。然而,观察到正常细胞 MCF10A 比癌细胞 MDA-MB-231 对 NTP 诱导的 ROS 毒性更敏感。当在 NTP 处理中使用 5mM 的 ROS 抑制剂 N-乙酰半胱氨酸(NAC)时,正常乳腺细胞 MCF10A 的增殖恢复。同时,NTP 作用仍然显著抑制 MDA-MB-231 细胞。我们的结果进一步表明,NTP 可以通过抑制白细胞介素 6 受体(IL-6R)通路诱导 MDA-MB-231 细胞凋亡。此外,NTP 抗癌选择性的机制与 NTP 特别是在 MCF10A 细胞中持续激活 HER2/Akt 有关,但在 MDA-MB-231 细胞中没有。因此,NTP 处理在 TNBC 和同源正常细胞中诱导的这两条不同的细胞信号通路使 NTP 成为未来治疗的潜在工具。