Abstract
Abstract Background: The final treatment for castration-resistant prostate cancer (CRPC) is generally cabazitaxel treatment. However, once CRPC becomes resistant to cabazitaxel, 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. We already established paclitaxel/docetaxel-resistant prostate cancer, PC-3-TxR and DU145-TxR cells, and characterized those cell lines previously. Then we further tried to establish cabazitaxel-resistant prostate cancer cell lines, and characterized those cell lines. Materials and Methods: We established two cabazitaxel-resistant cell lines, PC-3-TxR/CxR and DU145-TxR/CxR by increasing concentration of cabazitaxel from 1 nM to 30 nM gradually when PC-3-TxR and DU145-TxR cells were passaged. We confirmed the IC50 of docetaxel and cabazitaxel of these cells. Next we purified total RNA and performed cDNA microarray (Agilent and compared gene expression profiles among these cells. Results and Conclusion: IC50 of PC-3-TxR and PC-3-TxR/CxR for cabazitaxel was 1.3 nM and 15.4 nM, respectively. IC50 of DU145-TxR and DU145-TxR/CxR was 7.0 nM and 30. 8 nM, respectively. 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 4,470 genes in PC-3-TxR/CxR, and 1,345 genes in DU145-TxR/CxR cells were upregulated more than 3-fold and 4,683 genes PC-3-TxR/CxR and 1,537 genes were downregulated less than 0.3-fold, respectively. Especially, although expression of ABCB1 (MDR) gene was upregulated in DU145-TxR by 500-fold compared with DU145 cells, it was not upregulated in not upregulated in DU145-TxR/CxR cells any more. In contrast, expression of ABCB1 gene was upregulated in PC-3-TxR by 20-fold compared with PC-3 cells and it was further upregulated in PC-3-TxR/CxR by 40-fold compared with PC-3-TxR. In conclusion, various genes were regulated in cabazitaxel-resistant PCa cells and different mechanisms might be involved in this resistance in different cell lines. Citation Format: Atsushi Mizokami, Kazuaki Machioka, Kouji Izumi, Maolake Aerken, Ariunbold Natsagdorji, Yoshifumi Kadono, Yuta Takezawa, Hiroaki Iwamoto, Evan T. Keller. Establishment of cabazitaxel-resistant prostate cancer cell lines [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 85. doi:10.1158/1538-7445.AM2017-85
Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
