Journal of Shandong University (Health Sciences) ›› 2021, Vol. 59 ›› Issue (6): 103-110.doi: 10.6040/j.issn.1671-7554.0.2020.1656

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Silencing PRRX1 gene expression enhances the sensitivity of prostate cancer resistant cell line PC-3/DTX to docetaxel

XU Bing1, LI Yong2, LIU Ming1, LIU Yonghui1   

  1. 1. Department of Urology, The Third Affiliated Hospital of Nanhua University, Hengyang 421900, Hunan, China;
    2. Department of Urology, The Second Affiliated Hospital of Nanhua University, Hengyang 421900, Hunan, China
  • Published:2021-06-10

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Abstract: Objective To explore the effects of paired-related homeobox 1(PRRX1)gene silencing on the sensitivity of drug-resistant prostate cancer cells to docetaxel(DTX)and the possible mechanism. Methods The cancer tissues of 35 patients who were DTX chemotherapy sensitive(DTX-S)and 29 patients who were DTX chemotherapy resistant(DTX-R)were collected. The mRNA expression of PRRX1 in cancer tissues was detected with qRT-PCR. Human prostate cancer PC-3 cells were cultured in vitro, and the DTX-resistant cell line PC-3/DTX was established by increasing DTX concentration intermittently. The mRNA and protein expressions of PRRX1 in the drug-resistant PC-3/DTX and the parental PC3 cells were detected with qRT-PCR and Western blotting. The expression of PRRX1 gene in PC-3/DTX cells was silenced by siRNA, and the mRNA and protein expressions of PRRX1 in PC-3/DTX cells after transfection were detected with qRT-PCR and Western blotting. After DTX intervention, PC-3/DTX cells were transfected for 24 hours. The cell proliferation was detected with MTT, and the half inhibitory concentration(IC50)and drug resistance index(RI)were calculated. The cell apoptosis was detected with flow cytometry. The protein expressions of cleaved caspase-3, p-mTOR, mTOR, Beclin-1 and LC-3 were detected with Western blotting. Results The mRNA expression of PRRX1 in DTX-R cancer was higher than that in DTX-S cancer(6.59±1.49 vs 1.07±0.34)(F=656.401, P<0.05). The IC50 values of the drug-resistant cell line PC-3/DTX and the parental PC-3 cells treated with different concentrations of DTX for 24 h were(89.88±6.86)nmol/L and(15.56±1.45)nmol/L, respectively, and the RI was 5.78. The mRNA and protein expressions of PRRX1 in the drug-resistant cell line PC-3/DTX were higher than those in the parental PC-3 cells(mRNA: 9.22±1.50 vs 1.00±0.17; protein: 0.50±0.04 vs 0.08±0.02)(FmRNA=59.05, Fprotein=171.70, P<0.05). After the PRRX1 gene was silenced, the mRNA and protein expressions of PRRX1 in PC-3/DTX cells reduced(mRNA: 1.01±0.02 vs 0.98±0.04 vs 0.22±0.10; protein: 0.62±0.01 vs 0.61±0.01 vs 0.11±0.01)(FmRNA=122.01, Fprotein=554.53, P<0.05). Silencing the PRRX1 gene reduced the resistance of PC-3/DTX cells to DTX, promoted cell apoptosis, and up-regulated the expressions of p-mTOR and cleaved caspase-3, and down-regulated the protein expressions of Beclin-1 and LC-3(P<0.05). Conclusion Silencing the expression of the PRRX1 gene can enhance the sensitivity of the prostate cancer drug-resistant cell line PC-3/DTX to DTX, and the mechanism may be related to the activation of the mTOR signaling pathway to inhibit autophagy.

Key words: Gene silencing, Paired related homeobox 1, Prostate cancer, Docetaxel, Drug resistance, Autophagy

CLC Number: 

  • R737.1
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