Autophagy is a double-edged sword that affects
tumor progression by promoting cell survival or death depending on different living contexts. The concrete mechanism by which autophagy modulates the efficacy of
radiotherapy for
prostate cancer (PC) remains unclear. We exposed RM-1 PC cells to X-ray and explored the role of autophagy in
radiation injury. Our results showed increased apoptosis and autophagy levels in RM-1 cells after radiation. Pharmacological inhibition of autophagy by
chloroquine significantly mitigated radiation-induced apoptosis, while the enhancement of autophagy by
rapamycin aggravated apoptosis.
Sirt1, a member of
sirtuin family, deacetylates various
transcription factors to trigger cell survival in response to
radiation injury. We found that radiation led to
Sirt1 downregulation, which was reversed by the inhibition of autophagy. On the contrary, enhanced autophagy further diminished
protein level of
Sirt1. Notably, overexpression of
Sirt1 by plasmid significantly alleviated radiation-induced apoptosis, but silenced
Sirt1 by
siRNA further induced apoptosis, indicating the radioprotective effect of
Sirt1 on RM-1 cells. In summary, our findings suggested that autophagy-mediated
Sirt1 downregulation might be a promising therapeutic target for PC.