CCL2 induces resistance to the antiproliferative effect of cabazitaxel in prostate cancer cells

• DOI: 10.1111/cas.13876
• Publication Date: 2018-11-14T07:35:12Z
• Authors: Ariunbold Natsagdorj; Kouji Izumi; Kaoru Hiratsuka; Kazuaki Machioka; Hiroaki Iwamoto; Renato Naito; Tomoyuki Makino; Suguru Kadomoto; Kazuyoshi Shigehara; Yoshifumi Kadono; Wen‐Jye Lin; Aerken Maolake; Atsushi Mizokami
• Keywords: DU145; Cabazitaxel

Understanding the mechanism of chemoresistance and disease progression in patients with prostate cancer is important for developing novel treatment strategies. In particular, resistance to cabazitaxel a major challenge docetaxel‐resistant castration‐resistant (CRPC) because often administered as last resort. However, by which develops still unclear. C‐C motif chemokine ligands (CCL) were shown contribute castration cells via an autocrine mechanism. Therefore, we focused on CCL key factors cells. We previously established cabazitaxel‐resistant cell line, DU145‐TxR/CxR, from paclitaxel‐resistant DU145‐TxR. cDNA microarray analysis revealed that expression CCL2 was upregulated both DU145‐TxR DU145‐TxR/CxR compared DU145 The secreted protein level also higher than parental stimulation increased proliferation rate under treatments cabazitaxel, CCR2 (a specific receptor CCL2) antagonist suppressed cabazitaxel. CCL2‐CCR2 axis decreased apoptosis through inhibition caspase‐3 poly(ADP‐ribose) polymerase (PARP). apparently contributor Inhibition may be potential therapeutic strategy against chemoresistant CRPC combination