P4HB knockdown induces human HT29 colon cancer cell apoptosis through the generation of reactive oxygen species and inactivation of STAT3 signaling

Zhou,Ying; Yang,Jing; Zhang,Qilin; Xu,Qihua; Lu,Lihua; Wang,Jiening; Xia,Wei

doi:10.3892/mmr.2018.9660

P4HB knockdown induces human HT29 colon cancer cell apoptosis through the generation of reactive oxygen species and inactivation of STAT3 signaling

Authors:
- Ying Zhou
- Jing Yang
- Qilin Zhang
- Qihua Xu
- Lihua Lu
- Jiening Wang
- Wei Xia
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Affiliations: Department of Gastroenterology, Seventh People's Hospital of Shanghai University of Traditional Chinese Medicine, Shanghai 200137, P.R. China , Department of General Surgery, Seventh People's Hospital of Shanghai University of Traditional Chinese Medicine, Shanghai 200137, P.R. China , Department of Neurosurgery, Seventh People's Hospital of Shanghai University of Traditional Chinese Medicine, Shanghai 200137, P.R. China , Department of Integrated TCM and Western Medicine, President's Office, Seventh People's Hospital of Shanghai University of Traditional Chinese Medicine, Shanghai 200137, P.R. China, Department of Nuclear Medicine, Seventh People's Hospital of Shanghai University of Traditional Chinese Medicine, Shanghai 200137, P.R. China
Published online on: November 15, 2018 https://doi.org/10.3892/mmr.2018.9660
Pages: 231-237
Copyright: © Zhou et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Colon cancer is the second most lethal malignancy worldwide. A better understanding of colon cancer at the molecular level may increase overall survival rates. Previous studies have indicated that prolyl 4‑hydroxylase, β polypeptide (P4HB) is associated with tumorigenesis in colon cancer; however, its role and molecular mechanisms in colon cancer remain unclear. In the present study, the cellular responses to P4HB in human colon cancer cell lines were investigated by proliferation and apoptosis assays, western blotting, and immunohistochemistry. The results showed that expression of P4HB was higher in colon cancer tissues compared within adjacent normal tissues. P4HB knockdown increased the apoptosis of human HT29 cells. Furthermore, P4HB knockdown reduced the activation of signal transducer and activator of transcription 3 (STAT3) and promoted accumulation of reactive oxygen species (ROS). Inhibiting the accumulation of ROS abrogated the increased cell apoptosis induced by P4HB knockdown. Notably, decreased ROS levels effectively antagonized the effects of P4HB on STAT3 inactivation. In conclusion, these findings suggested that P4HB knockdown may induce HT29 human colon cancer cell apoptosis through the generation of ROS and inactivation of the STAT3 signaling pathway.

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