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.
Highlights
Renal cell carcinoma (RCC) is the most common form of kidney cancer and represents more than 90% of the solid malignant masses observed in the kidney [1]
The results indicate the stable 786-O cell line with low-expression of Ku80 was successfully generated by retrovirus-mediated method
Hyperthermia has become the fifth method of therapy after surgery, chemotherapy, radiation and biological therapy, and plays an important role in multidiscipline therapy for cancer
Summary
Renal cell carcinoma (RCC) is the most common form of kidney cancer and represents more than 90% of the solid malignant masses observed in the kidney [1]. RCC treatment is still a very challenging task due to no effective strategy in treating the late stages of this disease, so it is usually followed by a poor prognosis. It is essential to develop more effective therapeutic strategies for RCC. Hyperthermia is a therapeutic procedure that increases the temperature in body tissues in order to change the function of the cellular structures. In the past two decades, there has been a great interest in application of hyperthermia in conjunction with irradiation or/and chemotherapy in cancer treatment. The promising results from recent clinical trials indicate the effectiveness of hyperthermia treatment as an adjunct to radiotherapy or chemotherapy in treating
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