Cisplatin-induced CCL5 secretion from CAFs promotes cisplatin-resistance in ovarian cancer via regulation of the STAT3 and PI3K/Akt signaling pathways

被引：90

作者：

Zhou, Bo ^{[1
]}

Sun, Chaoyang ^{[1
]}

Li, Na ^{[1
]}

Shan, Wanying ^{[1
]}

Lu, Hao ^{[1
]}

Guo, Lili ^{[1
]}

Guo, Ensong ^{[1
]}

Xia, Meng ^{[1
]}

Weng, Danhui ^{[1
]}

Meng, Li ^{[1
]}

Hu, Junbo ^{[1
]}

Ma, Ding ^{[1
]}

Chen, Gang ^{[1
]}

机构：

[1] Huazhong Univ Sci & Technol, Tongji Med Coll, Tongji Hosp, Canc Biol Res Ctr, Wuhan 430030, Hubei, Peoples R China

来源：

INTERNATIONAL JOURNAL OF ONCOLOGY | 2016年 / 48卷 / 05期

关键词：

ovarian cancer; cancer-associated fibroblasts; cisplatin resistance; STAT3; p-Akt; cisplatin-induced chemokine (C-C motif) ligand 5; GROWTH-FACTOR; LUNG-CANCER; SURVIVIN EXPRESSION; ELEVATED LEVELS; RANTES LEVELS; CELL-LINE; BREAST; METASTASIS; APOPTOSIS; CHEMOTHERAPY;

D O I：

10.3892/ijo.2016.3442

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

Currently, acquired resistance to cisplatin (DDP) is a substantial obstacle to reducing the morbidity and mortality due to ovarian malignant tumors. Nevertheless, cisplatin plays a vital role in killing the tumor cells while it may also be a 'primer' involved in chemotherapy resistance. We found that the cisplatin-induced chemokine (C-C motif) ligand 5 (CCL5) secretion derived from cancer-associated fibroblasts (CAFs) promoted ovarian cancer cell resistance to cisplatin. Via a cytokine chip assay, we identified a spectrum of secreted proteins that were derived from the CAFs through cisplatin-induced treatment. Among these, CCL5 significantly attenuated the cytotoxic effect of cisplatin chemotherapy in vitro and in vivo. Additionally, CCL5 expression was also detected in 62 serous ovarian cancer patient tissue specimens using IHC, and the results demonstrated that chemotherapy resistant patients displayed higher expression of CCL5 than the chemo-sensitive patients (P<0.05). Mechanistically, we found that CCL5 notably increased STAT3 and Akt phosphorylation levels in ovarian cancer cells. These results indicated that cisplatin-induced CCL5 secretion derived from the CAFs may promote cisplatin resistance, which was mediated by regulation of the STAT3 and PI3K/Akt signal pathways.

引用

页码：2087 / 2097

页数：11

共 48 条

[41] Transcriptional regulation of the human osteopontin promoter: functional analysis and DNA-protein interactions [J].