RNA silencing of integrin-linked kinase increases the sensitivity of the A549 lung cancer cell line to cisplatin and promotes its apoptosis

Zhao,Xiaozhen; Xu,Zhenye; Wang,Zhongqi; Wu,Zhonghua; Gong,Yabin; Zhou,Lijuan; Xiang,Yi

doi:10.3892/mmr.2015.3471

RNA silencing of integrin-linked kinase increases the sensitivity of the A549 lung cancer cell line to cisplatin and promotes its apoptosis

Authors:
- Xiaozhen Zhao
- Zhenye Xu
- Zhongqi Wang
- Zhonghua Wu
- Yabin Gong
- Lijuan Zhou
- Yi Xiang
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Affiliations: Department of Oncology, Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai 200032, P.R. China, Experiment Center for Science and Technology, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, P.R. China
Published online on: March 11, 2015 https://doi.org/10.3892/mmr.2015.3471
Pages: 960-966
Copyright: © Zhao et al. This is an open access article distributed under the terms of Creative Commons Attribution License [CC BY_NC 3.0].

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Abstract

The expression of integrin‑linked kinase (ILK) has been reported to be involved in the regulation of integrin‑mediated processes, including cancer cell proliferation, migration and invasion. Previous studies have demonstrated that inhibition of ILK may be an underlying approach for treating cancer. However, whether the knock down of ILK affects growth and apoptosis of lung cancer cells remains to be elucidated. Importantly, whether downregulation of ILK increases the sensitivity of lung cancer cells to cisplatin and amplifies cell apoptosis also remains to be elucidated. In the present study, ILK downregulation was mediated by lentivirus‑mediated RNA interference. The expression levels of associated genes were determined by reverse‑transcription quantitative polymerase chain reaction and western blotting. Cell proliferation was evaluated using a modified 3‑(4,5‑dimethylthiazol‑2‑yl)‑2,5‑diphenyltetrazolium bromide assay and clone formation assay. The cell cycle and apoptosis were analyzed using flow cytometry. The current data revealed that lentivirus‑mediated ILK gene silencing alone inhibited A549 cell proliferation and promotes cell cycle arrest, however, had no detectable effect on cell apoptosis. However, combined treatment with lentivirus‑mediated ILK interference and cisplatin chemotherapy induced significantly more cell apoptosis than mono‑chemotherapy or knockdown. The increased cell apoptosis and proliferation inhibition were attributed to abnormal downstream protein expression of ILK, including phospho‑glycogen synthase kinase 3β, p‑AKT, activator protein‑1, β‑catenin, cyclin D1 and matrix metalloproteinase‑9. ILK inhibition may suppress the proliferation of A549 and increase A549 sensitivity to cisplatin. The combined treatment of ILK gene knockdown and chemotherapy has the potential to improve anticancer efficacy.

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