Authors: Yuichiro Matsuoka, Hideki Nakayama, Ryoji Yoshida, Akiyuki Hirosue, Masashi Nagata, Takuya Tanaka, Kenta Kawahara, Junki Sakata, Hidetaka Arita, Hikaru Nakashima, Satoru Shinriki, Daiki Fukuma, Hidenao Ogi, Akimitsu Hiraki, Masanori Shinohara, Ryo Toya, Ryuji Murakami
Summary:
Background: 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.
Methods: 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.
Results: 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.
Conclusions: 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.
Source:
British Journal of Cancer; 2016, 115 (10): 1234