卡巴齐塔塞尔
PI3K/AKT/mTOR通路
DU145型
蛋白激酶B
MAPK/ERK通路
癌症研究
前列腺癌
细胞生长
化学
细胞周期
细胞培养
药理学
信号转导
细胞
生物
细胞生物学
医学
癌症
内科学
生物化学
雄激素剥夺疗法
LNCaP公司
遗传学
作者
Hiroshi Hongo,Takeo Kosaka,Mototsugu Oya
出处
期刊:Cancer Science
[Wiley]
日期:2018-08-06
卷期号:109 (9): 2937-2945
被引量:31
摘要
Abstract Cabazitaxel (CBZ) is approved for docetaxel‐resistant castration‐resistant prostate cancer (CRPC). However, efficacy of CBZ for CRPC is limited and there are no effective treatments for CBZ‐resistant CRPC. In order to investigate the CBZ‐resistant mechanism, the establishment of a CBZ‐resistant cell line is urgently needed. We established CBZ‐resistant CRPC cell lines DU145CR and PC3CR by incubating DU145 and PC3 cells with gradually increasing concentrations of CBZ for approximately 2 years. We analyzed the gene expression profiles and cell cycle changes using microarray and flow cytometry. Pathway analysis revealed DU145CR cells had enhanced gene clusters of cell division and mitotic nuclear division. Enhancement of ERK signaling was detected in DU145CR cells. DU145CR cells had resistance to G 2 /M arrest induced by CBZ through ERK signaling activation. The MEK inhibitor PD184352 significantly inhibited cell proliferation of DU145CR. In contrast to DU145CR, PC3CR cells had enhancement of PI3K/AKT signaling. The PI3K/mTOR inhibitor NVP‐BEZ 235 had a significant antitumor effect in PC3CR cells. Cabazitaxel ‐resistant CRPC cells established in our laboratory had enhancement of cell cycle progression signals and resistance to G 2 /M arrest induced by CBZ. Enhancement of ERK signaling or PI3K/AKT signaling were detected in the cell lines, so ERK or PI3K/AKT could be therapeutic targets for CBZ‐resistant CRPC.
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