IL-6 controls resistance to radiation by suppressing oxidative stress via the Nrf2-antioxidant pathway in oral squamous cell carcinoma.
IL-6 controls resistance to radiation by suppressing oxidative stress via the Nrf2-antioxidant pathway in oral squamous cell carcinoma.
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DOI：
10.1038/bjc.2016.327
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发表时间：
2016-11-08
影响因子：
8.8
通讯作者：
Murakami, Ryuji
中科院分区：
文献类型：
--
作者：
Matsuoka, Yuichiro;Nakayama, Hideki;Yoshida, Ryoji;Hirosue, Akiyuki;Nagata, Masashi;Tanaka, Takuya;Kawahara, Kenta;Sakata, Junki;Arita, Hidetaka;Nakashima, Hikaru;Shinriki, Satoru;Fukuma, Daiki;Ogi, Hidenao;Hiraki, Akimitsu;Shinohara, Masanori;Toya, Ryo;Murakami, Ryuji
关键词：
在促进肿瘤恶性程度方面，IL-6信号传导被认为具有重要作用。然而，IL-6在口腔鳞状细胞癌（OSCC）放射敏感性中的生物学作用仍不清楚。本研究旨在探讨IL-6对口腔鳞癌放射敏感性的影响及其分子机制。使用两种OSCC细胞系和具有抗辐射细胞的OSCC组织样品。我们研究了IL-6或托珠单抗（一种人源化抗人IL-6受体抗体）或两者对体外X射线照射后放射敏感性和DNA损伤的影响。此外，我们研究了参与的Nrf 2-抗氧化剂途径IL-6介导的放射抗性机制，使用口腔鳞癌细胞系和组织。IL-6水平的增加抑制了辐射诱导的细胞死亡，并且托珠单抗对IL-6信号传导的阻断使肿瘤细胞对辐射敏感。IL-6的抗辐射作用与减少辐射后DNA损伤有关。我们还发现，IL-6不仅促进下游分子STAT 3的激活，而且还促进Nrf 2-抗氧化剂途径的激活，通过上调Mn-SOD导致氧化应激的显著降低。这些结果表明，IL-6信号的阻断结合常规放疗可以提高放射抵抗性口腔鳞癌患者的治疗反应和生存率。
In promoting tumour malignancy IL-6 signalling is considered to have an important role. However, the biological roles of IL-6 on radiosensitivity in oral squamous cell carcinoma (OSCC) remain largely unclear. The objective of this study is to determine the effects and molecular mechanisms of IL-6 on radiosensitivity in OSCC. Two OSCC cell lines, and OSCC tissue samples with radioresistant cells were used. We examined the effects of IL-6, or tocilizumab, a humanised anti-human IL-6 receptor antibody, or both on radiosensitivity and DNA damage after X-ray irradiation in vitro. In addition, we investigated the involvement of the Nrf2-antioxidant pathway in IL-6-mediated radioresistant mechanisms using OSCC cell lines and tissues. Increased levels of IL-6 suppressed radiation-induced cell death, and the blockade of IL-6 signalling by tocilizumab sensitised tumour cells to radiation. The radioresistant effect of IL-6 was associated with decreased DNA damage after radiation. We also found that IL-6 promotes the activation of not only the downstream molecule STAT3 but also the Nrf2-antioxidant pathway, leading to a significant decrease in oxidative stress by upregulating Mn-SOD. These results indicate that the blockade of IL-6 signalling combined with conventional radiotherapy could augment the treatment response and survival rate in patients with radioresistant OSCC.
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影响因子：
3.8
作者：
Nakashima H;Matsuoka Y;Yoshida R;Nagata M;Hirosue A;Kawahara K;Sakata J;Arita H;Hiraki A;Nakayama H
通讯作者：
Nakayama H
影响因子：
5.7
作者：
Kuwahara, Yoshikazu;Li, Li;Fukumoto, Manabu
通讯作者：
Fukumoto, Manabu
影响因子：
2
作者：
Kuwahara, Yoshikazu;Mori, Miyuki;Fukumoto, Manabu
通讯作者：
Fukumoto, Manabu
影响因子：
21.3
作者：
Komatsu, Masaaki;Kurokawa, Hirofumi;Yamamoto, Masayuki
通讯作者：
Yamamoto, Masayuki
影响因子：
3.6
作者：
Fisher CJ;Goswami PC
通讯作者：
Goswami PC