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

  • Authors:
    • Bo Zhou
    • Chaoyang Sun
    • Na Li
    • Wanying Shan
    • Hao Lu
    • Lili Guo
    • Ensong Guo
    • Meng Xia
    • Danhui Weng
    • Li Meng
    • Junbo Hu
    • Ding Ma
    • Gang Chen
  • View Affiliations

  • Published online on: March 15, 2016     https://doi.org/10.3892/ijo.2016.3442
  • Pages: 2087-2097
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Abstract

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.
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May-2016
Volume 48 Issue 5

Print ISSN: 1019-6439
Online ISSN:1791-2423

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Spandidos Publications style
Zhou B, Sun C, Li N, Shan W, Lu H, Guo L, Guo E, Xia M, Weng D, Meng L, Meng L, et al: Cisplatin-induced CCL5 secretion from CAFs promotes cisplatin-resistance in ovarian cancer via regulation of the STAT3 and PI3K/Akt signaling pathways. Int J Oncol 48: 2087-2097, 2016.
APA
Zhou, B., Sun, C., Li, N., Shan, W., Lu, H., Guo, L. ... Chen, G. (2016). Cisplatin-induced CCL5 secretion from CAFs promotes cisplatin-resistance in ovarian cancer via regulation of the STAT3 and PI3K/Akt signaling pathways. International Journal of Oncology, 48, 2087-2097. https://doi.org/10.3892/ijo.2016.3442
MLA
Zhou, B., Sun, C., Li, N., Shan, W., Lu, H., Guo, L., Guo, E., Xia, M., Weng, D., Meng, L., Hu, J., Ma, D., Chen, G."Cisplatin-induced CCL5 secretion from CAFs promotes cisplatin-resistance in ovarian cancer via regulation of the STAT3 and PI3K/Akt signaling pathways". International Journal of Oncology 48.5 (2016): 2087-2097.
Chicago
Zhou, B., Sun, C., Li, N., Shan, W., Lu, H., Guo, L., Guo, E., Xia, M., Weng, D., Meng, L., Hu, J., Ma, D., Chen, G."Cisplatin-induced CCL5 secretion from CAFs promotes cisplatin-resistance in ovarian cancer via regulation of the STAT3 and PI3K/Akt signaling pathways". International Journal of Oncology 48, no. 5 (2016): 2087-2097. https://doi.org/10.3892/ijo.2016.3442