Overexpression of PER3 reverses paclitaxel resistance of prostate cancer cells by inhibiting the Notch pathway

D.-W. Cai, D. Chen, S.-P. Sun, Z.-J. Liu, F. Liu, S.-Z. Xian, P.-S. Wu, G.-Q. Kong

Department of Urology, Beijing Luhe Hospital, Capital Medical University, Beijing, China. kongguangqi@126.com

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• Oncology

OBJECTIVE: To investigate the levels of period circadian protein homolog 3 (PER3) in paclitaxel-resistant prostate cancer patients and the effect of PER3 on paclitaxel-resistant prostate cancer cell lines.

PATIENTS AND METHODS: A total of 38 patients diagnosed with prostate cancer in our hospital from June 2013 to June 2016 were divided into paclitaxel-resistant group (n=19) and non-resistant group (n=19) according to the follow-up treatment effects. Fluorescent quantitative polymerase chain reaction (PCR) was performed to evaluate the levels of PER3 in drug-resistant and non-resistant groups as well as the relative levels of PER3 before and after treatment. PER3 was overexpressed or knocked down in a paclitaxel-resistant prostate cancer cell line, followed by measuring its IC50 as well as changes in cell cycle and apoptosis. Using Western blot, we detected downregulation of Notch pathway and related receptor proteins when PER3 was overexpressed.

RESULTS: The results of fluorescence quantitative PCR showed that the expression of PER3 in the paclitaxel-resistant prostate cancer group was lower than that in the non-resistant group, and the relative expression of PER3 was decreased after treatment. Fluorescent quantitative PCR and Western blot showed that the expression of PER3 in paclitaxel-resistant prostate cancer cells was higher than that of the untreated counterparts. After overexpression of PER3 by transfecting prostate cancer-resistant cell lines with plasmids, the IC50 was significantly reduced, the cell cycle was arrested, and the apoptosis was significantly increased. Subsequently, we detected decreased expression of Notch1 in PER3 over-expressed paclitaxel-resistant cell lines by Western blot; this attenuated resistance in paclitaxel-resistant cell lines.

CONCLUSIONS: PER3 can induce sensitivity of paclitaxel-resistant cell lines to paclitaxel by inhibiting the expression of Notch1.

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