Adipocytes induce the resistance of ovarian cancer to carboplatin through ANGPTL4

Zhou,Songhui; Wang,Ruicheng; Xiao,Hong

doi:10.3892/or.2020.7647

Adipocytes induce the resistance of ovarian cancer to carboplatin through ANGPTL4

Authors:
- Songhui Zhou
- Ruicheng Wang
- Hong Xiao
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Affiliations: Department of Pharmacy, Jiangsu Cancer Hospital and Jiangsu Institute of Cancer Research and The Affiliated Cancer Hospital of Nanjing Medical University, Nanjing, Jiangsu 210029, P.R. China, Department of Pharmacy, The Affiliated Brain Hospital of Nanjing Medical University, Nanjing, Jiangsu 210029, P.R. China
Published online on: June 16, 2020 https://doi.org/10.3892/or.2020.7647
Pages: 927-938
Copyright: © Zhou et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

The resistance of cancer cells to carboplatin restricts their efficacy in the clinical setting, and a solution to reverse the resistance is urgently required for the treatment of ovarian cancer. An increasing number of studies have found associations between obesity and the incidence, and mortality rates of female cancer. However, the association between adipocytes and the resistance of ovarian cancer has rarely been reported. Based on this, the present study first revealed the inductive effect of adipocytes on the resistance of ovarian cancer to carboplatin using in vivo and in vitro experiments. Subsequently, it was identified that the angiopoietin‑like 4 (ANGPTL4) secreted by adipocytes played a vital role in the resistance of ovarian cancer using bioinformatics analysis, cellular and molecular biological experiments, as well as forward and backward validation. The glycosylated ANGPTL4 protein could bind with integrin α5β1 on the surface of ovarian cancer cells; following which, it could activate the c‑myc/NF‑κB pathway and stimulate the expression of the antiapoptotic protein Bcl‑xL, as well as the ABC transporter family members ABCB1, ABCC1 and ABCG2. Thus, inducing the resistance of ovarian cancer to carboplatin. In conclusion, targeting the adipocyte‑derived ANGPTL4 combined with the application of carboplatin contributes to the clinical treatment for ovarian cancer.

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