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Atorvastatin Enhances Effects of Radiotherapy on Prostate Cancer Cells and Xenograft Tumor Mice Through Triggering Interaction Between Bcl-2 and MSH2

Zhenhua He, Jingmin Yuan, Fuhui Shen, Fangang Zeng, Ping Qi, Zhiping Wang, Zhenxing Zhai

Department of Neurosurgery, Lanzhou University Second Hospital, Lanzhou, Gansu, China (mainland)

Med Sci Monit 2020; 26:e923560

DOI: 10.12659/MSM.923560

Available online: 2020-07-03

Published: 2020-09-01

BACKGROUND: Prostate cancer (PCa) is considered to be the 4th most common cancer in males in the world. This study aimed to explore effects of atorvastatin on colony formation of PCa cells and radio-resistance of xenograft tumor models.
MATERIAL AND METHODS: PCa cell lines, including PC3, DU145, and Lncap, were treated with irradiation (4 Gy) and/or atorvastatin (6 μg/mL). Cells were divided into tumor cell group, irradiation treatment group (IR group) and irradiation+atorvastatin treatment group (IR-AS group). Xenograft tumor mouse model was established. Plate clone formation assay (multi-target/single-hit model) was conducted to evaluate colony formation. Flow cytometry analysis was employed to detect apoptosis. Interaction between Bcl-2 and MSH2 was evaluated with immuno-fluorescence assay.
RESULTS: According to the plate colony formation assay and multi-target/single-hit model, IR-treatment significantly suppressed colony formation in PCa cells (including PC3, DU145, and Lncap cells) compared to no-IR treated cells (P<0.05). Atorvastatin remarkably enhanced inhibitive effects of irradiation on colony formation of PCa cells (P<0.05), however, the IR+AS group demonstrated no effects on apoptosis, comparing to IR group (P>0.05). Atorvastatin administration (IR+AS group) significantly reduced tumor size of IR-treated PCa cells-induced xenograft tumor mice (P<0.05). Bcl-2 interacted with MSH2 both in tumor tissues of xenograft tumor mice.
CONCLUSIONS: Atorvastatin administration inhibited colony formation in PCa cells and enhanced effects of radiotherapy on tumor growth of xenograft tumor mice, which might be associated with interaction between Bcl-2 and MSH2 molecule.

Keywords: beta-MSH, Drug Resistance, Prostatic Neoplasms, Radiotherapy