Abstract
Hypoxia could enhance radioresistance in prostate cancer cells through up-regulating HIF-1α, which could be inhibited by statins in several cancer cells. However, this effect of statins in prostate cancer remains unclear. In the present study, we aim to investigate the effect of atorvastatin on HIF-1α expression and radiosensitivity in prostate cancer cells. The hypoxia-induced human prostate cancer PC3 cells were generated by incubating with 5% O2 for 24 h. The cell viability and apoptosis were respectively analyzed by cell counting kit-8 (CCK-8) assay and flow cytometry. The HIF-1α protein expression was assessed by Western blotting. HIF-1α expression in PC3 cells was significantly increased after incubating with 5% O2 for 24 h. The viability of hypoxia-induced PC3 cells was inhibited by a higher dose of irradiation than control cells. The viability of hypoxia-induced PC3 cells were inhibited by astorvastatin with a higher concentration than control cells. Astorvastatin reduced the HIF-1α protein expression in hypoxia-induced PC3 cells, and induced apoptosis of both control and hypoxia-induced cells with and without irradiation. Atorvastatin could enhance radiosensitivity in hypoxia-induced prostate cancer cells, which may be related with inhibition of HIF-1α protein.
Highlights
Prostate cancer is the sixth leading cause of cancer deaths in males in the world [1]
The hypoxia-induced PC3 cells were obtained by incubating with 5% O2 for 24 h, since HIF-1α expression in PC3 cells was highest after incubating for 24 h
We found that hypoxia-induced prostate cancer PC3 cells were less radiosensitive than control cancer cells
Summary
Prostate cancer is the sixth leading cause of cancer deaths in males in the world [1]. Radiotherapy has been widely used as a curative treatment for prostate cancer [2]. Radiotherapy in prostate cancer has undergone significant advances in technology and clinical practice, which contributes to a better cancer control outcome and less treatment morbidity than before [3,4]. Prostate cancer radioresistance remains in a number of patients, leading to cancer relapse [5]. Radioresistance of prostate cancer may be mainly due to hypoxia in the center of tumors, which could induce a G2/M cell cycle arrest, inhibit apoptosis, and reduce the number of senescent cells [6]. Hypoxia-induced prostate cancer would be a key point in overcoming the radioresistance in prostate cancer
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