Establishment and characterization of two cabazitaxel-resistant prostate cancer cell lines
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Kazuaki Machioka1, Kouji Izumi1, Yoshifumi Kadono1, Hiroaki Iwamoto1, Renato Naito1, Tomoyuki Makino1, Suguru Kadomoto1, Ariunbold Natsagdorj1, Evan T. Keller2, Jian Zhang3 and Atsushi Mizokami1
1Department of Integrative Cancer Therapy and Urology, Graduate School of Medical Science, Kanazawa University, Kanazawa, 920-8640, Japan
2Department of Urology, School of Medicine and Biointerfaces Institute, University of Michigan, Ann Arbor, MI, 48109, USA
3Center for Translational Medicine, Guangxi Medical University, Medical Science Research Building, Nanning, Guangxi, 530021, P. R. China
Atsushi Mizokami, email: email@example.com
Keywords: prostate cancer; CRPC; cabazitaxel-resistant; MDR1
Received: January 11, 2018 Accepted: February 26, 2018 Epub: March 05, 2018 Published: March 23, 2018
Once castration-resistant prostate cancer (CRPC) become resistant for cabazitaxel treatment, the patients are obliged to best supportive care. Therefore, the elucidation of the mechanism of the cabazitaxel-resistance and the conquest are important themes to improve the prognosis of the patients. Then we tried to establish cabazitaxel-resistant CRPC cell lines and characterized them. We established two cabazitaxel-resistant cell lines, PC-3-TxR/CxR and DU145-TxR/CxR from PC-3-TxR and DU145-TxR cell lines previously we established. PC-3-TxR/CxR and DU145-TxR/CxR cells became resistant for cabazitaxel by 11.8-fold and 4.4-fold, respectively. The TxR/CxR cells showed cabazitaxel-resistant using SCID mice in vivo. Although expression of multi-drug resistance gene 1 (MDR1) was up-regulated in DU145-TxR compared with DU145 cells, it was not up-regulated in DU145-TxR/CxR cells any more. In contrast, expression of MDR1 gene was up-regulated in PC-3-TxR compared with PC-3 cells and it was further up-regulated in PC-3-TxR/CxR compared with PC-3-TxR cells. Comparison of cDNA microarray between PC-3-TxR and PC-3-TxR/CxR cells or between DU145-TxR and DU145-TxR/CxR cells revealed that many genes were up-regulated or down-regulated. Finally, knockdown of MDR1 recovered the sensitivity to cabazitaxel not only in PC-3-TxR/CxR cells but also DU145-TxR/CxR cells. Together, regulation of MDR1 gene is important for conquest of the cabazitaxel-resistance.
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