Abstract
Recurrent liver cancer after surgery is often treated with radiotherapy, which induces liver damage. It has been documented that activation of the TGF-β and NF-κB signaling pathways plays important roles in irradiation-induced liver pathologies. However, the significance of mTOR signaling remains undefined after irradiation exposure. In the present study, we investigated the effects of inhibiting mTORC1 signaling on irradiated livers. Male C57BL/6J mice were acutely exposed to 8.0 Gy of X-ray total body irradiation and subsequently treated with rapamycin. The effects of rapamycin treatment on irradiated livers were examined at days 1, 3, and 7 after exposure. The results showed that 8.0 Gy of irradiation resulted in hepatocyte edema, hemorrhage, and sinusoidal congestion along with a decrease of ALB expression. Exposure of mice to irradiation significantly activated the mTORC1 signaling pathway determined by pS6 and p-mTOR expression via western blot and immunostaining. Transient inhibition of mTORC1 signaling by rapamycin treatment consistently accelerated liver recovery from irradiation, which was evidenced by decreasing sinusoidal congestion and increasing ALB expression after irradiation. The protective role of rapamycin on irradiated livers might be mediated by decreasing cellular apoptosis and increasing autophagy. These data suggest that transient inhibition of mTORC1 signaling by rapamycin protects livers against irradiation-induced damage.
Highlights
Liver cancer is one of the most common solid tumors in the world and results in a large amount of deaths (Ferlay et al, 2015)
We showed that the mTOR complex 1 (mTORC1) signaling pathway was activated by irradiation in liver, the functional significance of mTORC1 signaling remains obscure in liver recovery after radiation exposure
The liver is often considered to be radiosensitive. This observation is based on patients treated with liver irradiation when the liver was previously cirrhotic, or FIGURE 4 | Rapamycin treatment reduced the increase of phosphorylated S6 (pS6) expression in irradiated liver tissues. (A and B) Increased expression of pS6 and p-Mammalian target of rapamycin (mTOR) by irradiation was reduced through rapamycin (Rap) treatment
Summary
Liver cancer is one of the most common solid tumors in the world and results in a large amount of deaths (Ferlay et al, 2015). High recurrence occurs despite surgical treatment (Hsu et al, 2017). Radiotherapy is often considered for use when those patients with liver cancer have recurrence after surgery or are unfit for surgery (Ogata et al, 1963; Kalogeridi et al, 2015). Radiotherapy is an effective treatment to limit liver cancer growth and metastasis. Exposure of normal hepatic tissues to irradiation results in collateral liver injury, which limits the effectiveness of radiotherapy on liver cancer. 5–10% of patients will experience radiation-induced liver damage when they are exposed to a radiation dose up to 30 Gy. If the dose is increased to 43 Gy, 50% of patients will
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
