Role of Wnt/β‑catenin, Wnt/c‑Jun N‑terminal kinase and Wnt/Ca2+ pathways in cisplatin‑induced chemoresistance in ovarian cancer

Huang,Lu; Jin,Ye; Feng,Shujun; Zou,Yuqing; Xu,Sainan; Qiu,Shuang; Li,Ling; Zheng,Jianhua

doi:10.3892/etm.2016.3885

Role of Wnt/β‑catenin, Wnt/c‑Jun N‑terminal kinase and Wnt/Ca2+ pathways in cisplatin‑induced chemoresistance in ovarian cancer

Authors:
- Lu Huang
- Ye Jin
- Shujun Feng
- Yuqing Zou
- Sainan Xu
- Shuang Qiu
- Ling Li
- Jianhua Zheng
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Affiliations: Department of Obstetrics and Gynecology, The First Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang 150001, P.R. China, Department of Computing, Brain Cognition Computing Lab, University of Kent, Kent CT2 7NZ, UK
Published online on: November 8, 2016 https://doi.org/10.3892/etm.2016.3885
Pages: 3851-3858
Copyright: © Huang et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

The aim of the present study was to explore the expression of Wnt signaling proteins β-catenin, c-Jun N-terminal kinase (JNK) and Ca2+/calmodulin‑dependent protein kinase II (CaMKII) in ovarian cancer cells, and assess the correlation between this expression and cisplatin‑induced chemoresistance. SKOV3 ovarian carcinoma cells and SKOV3/DDP (cisplatin resistant) cells were treated with cisplatin in the absence or presence of a Wnt signaling activator (CHIR‑99021, glycogen synthase kinase 3β inhibitor) or inhibitor (XAV‑939, tankyrase inhibitor). Following incubation for 48 h, cell viability, proliferation and cytotoxicity were measured using a sensitive colorimetric cell counting kit. Expression levels of β‑catenin, JNK and CaMKII were detected by western blot and immunofluorescence staining. The results of the current study identified that β‑catenin and JNK expression levels were significantly higher (P<0.01 and P<0.05 respectively), while CaMKII expression was lower (P>0.05), in SKOV3/DDP cells compared with SKOV3 cells. Moreover, following treatment with 20 µM cisplatin, reduced expression of β‑catenin and JNK (P<0.05 and P<0.01 respectively), and increased expression of CaMKII (P<0.01), was observed in SKOV3 and SKOV3/DPP cell lines. Furthermore, inhibition of β‑catenin signaling by XAV‑939 effectively reversed cisplatin chemoresistance in SKOV3/DDP cells. Similarly, XAV‑939 downregulated JNK expression (P<0.001), but upregulated CaMKII expression (P<0.001), in SKOV3/DDP cells. In conclusion, abnormal activation of Wnt/β‑catenin and Wnt/JNK signaling pathways in ovarian cancer cells promotes cisplatin resistance, while the Wnt/Ca2+ signaling pathway reduces cisplatin resistance. This indicates that β‑catenin, JNK and CaMKII are potential therapeutic targets in chemoresistant ovarian cancers.

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