Hyperthermia Induces Apoptosis of 786-O Cells through Suppressing Ku80 Expression

PLoS One. 2015 Apr 22;10(4):e0122977. doi: 10.1371/journal.pone.0122977. eCollection 2015.

Abstract

Hyperthermia as an anticancer method has been paid increasing attention in recent years. Several studies have shown that hyperthermia can kill tumor cells by inducing apoptosis. However, the underlying molecular mechanisms of hyperthermia-induced apoptosis are largely unknown. To investigate the effects and molecular mechanism of hyperthermia on the apoptosis in renal carcinoma 786-O cells, we firstly examined apoptosis and Ku expression in 786-O cell line treated with heat exposure (42°C for 0-4 h). The results showed that hyperthermia induced apoptosis of 786-O cells, and suppressed significantly Ku80 expression, but not Ku70 expression. Next, we knock-down Ku80 in 786-O cells, generating stable cell line 786-O-shKu80, and detected apoptosis, cell survival and cell cycle distribution. Our data showed higher apoptotic rate and lower surviving fraction in the stable cell line 786-O-shKu80 compared with those in control cells, exposed to the same heat stress (42°C for 0-4 h). Moreover, the results also showed suppression of Ku80 led to G2/M phase arrest in the stable cell line 786-O-shKu80 following heat treatment. Together, these findings indicate that Ku80 may play an important role in hyperthermia-induced apoptosis and heat-sensitivity of renal carcinoma cells through influencing the cell cycle distribution.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antigens, Nuclear / genetics*
  • Apoptosis*
  • Carcinoma, Renal Cell / pathology*
  • Cell Cycle
  • Cell Line, Tumor
  • DNA-Binding Proteins / genetics*
  • Gene Expression Regulation, Neoplastic*
  • Hot Temperature
  • Humans
  • Hyperthermia, Induced*
  • Kidney Neoplasms / pathology*
  • Ku Autoantigen

Substances

  • Antigens, Nuclear
  • DNA-Binding Proteins
  • Xrcc6 protein, human
  • Ku Autoantigen

Grants and funding

This work was supported by grants from National Natural Science Foundation of China (No.30872142, No.81272350, No.81472999 to WJ), Natural Science Foundation of Guangdong (No.S2012010008908 to WJ, No. 8151012003000011 to DQ), University Talent Program of Guangzhou (No.12A015G to WJ) and Science and Technology Program of Guangdong (No.2010B060900096). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.