Enhancement of paclitaxel and carboplatin therapies by CCL2 blockade in ovarian cancers.
Enhancement of paclitaxel and carboplatin therapies by CCL2 blockade in ovarian cancers.
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DOI：
10.1016/j.molonc.2014.03.016
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发表时间：
2014-10
影响因子：
6.6
通讯作者：
Sikic BI
中科院分区：
文献类型：
--
作者：
Moisan F;Francisco EB;Brozovic A;Duran GE;Wang YC;Chaturvedi S;Seetharam S;Snyder LA;Doshi P;Sikic BI
卵巢癌与白细胞浸润和高水平的趋化因子如CCL2有关。我们验证了CCL2抑制可以增强卡铂和紫杉醇化疗的假说。3株紫杉醇耐药卵巢癌细胞株ES-2/TP、MES-OV/TP和OVCAR-3/TP的CCL2表达均高于亲本细胞。接种这些细胞的小鼠分别用抗人CCL2抗体CNTO 888和抗鼠MCP-1抗体C1142处理，加或不加紫杉醇或卡铂。我们的结果显示，CCL2阻滞剂对紫杉醇和卡铂的疗效有相加作用。这种治疗效果在很大程度上是由于抑制了小鼠间质CCL2。我们发现抑制CCL2可以加强紫杉醇和卡铂对卵巢癌的治疗。
Ovarian cancer is associated with a leukocyte infiltrate and high levels of chemokines such as CCL2. We tested the hypothesis that CCL2 inhibition can enhance chemotherapy with carboplatin and paclitaxel. Elevated CCL2 expression was found in three non-MDR paclitaxel resistant ovarian cancer lines ES-2/TP, MES-OV/TP and OVCAR-3/TP, compared to parental cells. Mice xenografted with these cells were treated with the anti-human CCL2 antibody CNTO 888 and the anti-mouse MCP-1 antibody C1142, with and without paclitaxel or carboplatin. Our results show an additive effect of CCL2 blockade on the efficacy of paclitaxel and carboplatin. This therapeutic effect was largely due to inhibition of mouse stromal CCL2. We show that inhibition of CCL2 can enhance paclitaxel and carboplatin therapy of ovarian cancer.