This indicates HSP70 is an important radiation-resistance gene. However, this result came from the non-tumor cell experiment. Herein, we used Hep-2 cell line, which has a high expression level of endogenous HSP70 protein, to establish a laryngeal carcinoma xenograft model. The selleck compound HSP70 antisense oligos was used to block HSP70 expression. Our results showed that HSP70 antisense oligos treatment increased radiation sensitizing activity in xenograft tumors. These results suggested that HSP70 may play an important role as a radiotherapy-resistant gene in laryngeal carcinoma. It has been shown HSP70 could interact with selleck chemicals nucleolin (C23) and inhibit

H2O2-induced cleavage and degradation of C23 [10]. C23, a nonhistone nuclear RNA binding protein, plays an important role in maintaining the CBL-0137 balance between anti-apoptosis and pro-apoptosis [8, 9]. Our study has shown that blocking HSP70 expression could promote cleavage and degradation the expression of C23 on laryngeal carcinoma xenograft after radiotherapy. Nucleolin was cleaved and degraded during several apoptotic cell models. Previous

studies have showed radiotherapy could induce a typical apoptotic cell death by breaking nucleolin into fragmentations [17, 18]. Western-blot results of the cleavage and degradation of nucleolin showed that a cleaved band (80 kDa) of nucleolin appeared after radiotherapy by a Cyclooxygenase (COX) single dose of 5Gy. Cleavage and degradation of nucleolin was also observed in both group antisense and group random which indicated that cleavage and degradation of nucleolin was a typical response to laryngeal carcinoma xenograft damage caused by the radiotherapy. The over-expression of HSP70 inhibited cleavage and degradation of nucleolin, and induced radiotherapy resistance. Taken

together, our data suggested that cleavage and degradation of nucleolin were involved in the apoptosis induced by radiotherapy, HSP70 serve as an radiotherapy resistance gene by inhibiting the cleavage and degradation of nucleolin. Since the complex nature of the mechanisms in apoptosis and the multi-functionality of HSP70, there are still several questions remain to be answered inorder to address the role of HSP70 in radiation resistance. One interesting question is which domain of HSP70 is involved in the cleavage and degradation of nucleolin. It will also be interesting to know if nucleolin plays an essential role in radiation induced apoptosis. A nucleolin overexpression and knock-out model will be highly valuable to address this issue. The role of each HSP70 functional domain in protecting C23 are still yet to be determined.