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Abstract
BackgroundRadiotherapy plays an important role in cancer therapy. However, the radioresistance of some human cancers, particularly renal carcinoma, often results in radiotherapy failure. The Ku protein is essential for the repair of a majority of DNA double-strand breaks in mammalian cells, but effect of Ku70 expression on radiosensitivity in renal carcinoma is unclear. Here, we investigate the impact of Ku70 on radiosensitivity in renal carcinoma cells through regulating the expression of Ku70.MethodsThe stable overexpression of Ku70 or suppression of Ku70 in renal carcinoma cell line (786-O) was generated by retrovirus-mediated Ku70 cDNA or shRNA targeting Ku70. Ku70 expression was determined by RT-PCR and Western blot analysis, the apoptosis of the stable cells was assayed with flow cytometry and TUNEL assay and the effect of radiation on the livability of stable cells was assessed by MTT assay.ResultsUp-regulation of Ku70 expression of 786-O cells could inhibit cell apoptosis and reduce susceptibility to radiation. On the contrary, 786-O cells with suppression of Ku70 expression could induce cell apoptosis and significantly enhance the sensitivity to radiation.ConclusionsThese findings indicated that Ku70 might play an important role in radioresistance of renal carcinoma, and inhibition of Ku70 can increase the radiosensitivity of 786-O cells by enhancing apoptosis, suggesting down-regulation of Ku70 expression combined with radiotherapy will be a potential strategy for renal cell carcinoma therapy.
Highlights
Radiotherapy plays an important role in cancer therapy
Ku70 expression in stable cell lines In order to construct the pBaBb-puro-Ku70 vector containing a Ku70 cDNA and the pSUPERretro-puro-siKu70 vector, a DNA fragment encoding Ku70 was amplified by PCR from human genomic DNA and three pairs of effective RNA interference sequences to target Ku70 gene were designed and synthesized
The results showed that up-regulation of Ku70 expression of 786-O cells could reduce the radiosensitivity to radiation; on the contrary, 786-O cells with suppression of Ku70 expression could result in increased radiosensitivity
Summary
Radiotherapy plays an important role in cancer therapy. the radioresistance of some human cancers, renal carcinoma, often results in radiotherapy failure. The Ku protein is essential for the repair of a majority of DNA double-strand breaks in mammalian cells, but effect of Ku70 expression on radiosensitivity in renal carcinoma is unclear. DNA double-strand breaks (DSBs) caused by endogenous (byproducts of cellular metabolism and replication associated errors) and exogenous (ionizing radiation and chemotherapeutic drugs) agents, are the most lethal damage among the different kind of DNA damages as unrepaired DSBs can result in genomic instability, cell death and tumorigenesis [3,4,5]. It can be repaired via two major pathways: homologous recombination (HR) and nonhomologous end joining (NHEJ).
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