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Knockdown of PLCε inhibits inflammatory cytokine release via STAT3 phosphorylation in human bladder cancer cells

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Tumor Biology

Abstract

Phospholipase Cε (PLCε) is a multifunctional enzyme implicated in inflammatory functions. There are limited data, however, on how PLCε can alter inflammatory cytokine by affecting downstream pathways. Recent studies suggest that inflammation is likely to have an important role in transitional cell carcinoma of bladder (TCCB) and cancer disease progression. Here, we showed that PLCε and p-STAT3 expression were both elevated in TCCB tissues compared to adjacent tissues, and the increase of PLCε level was associated with the increase of p-STAT3 level. Then, knockdown of PLCε using adenovirus-shPLCε significantly decreased inflammatory cytokine (IL-6, TNF-α, IL-1β) expression and inflammation-associated gene (TLR4, MyD88, p-STAT3) expression. Furthermore, we demonstrated that PLCε knockdown blocked LPS-induced inflammatory cytokine and p-STAT3 expression. Additionally, we found that combined treatment of STAT3 inhibitor S3I-201 with adenovirus-shPLCε exhibited synergistic inhibitory effects on expression of p-STAT3. Our results suggested that STAT3 phosphorylation is involved in PLCε-mediated inflammatory cytokine release. Our research is of potential importance in drug development programs using PLCε as a therapeutic target for TCCB.

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Acknowledgements

This work was supported by the National Natural Science Foundation of China (Grant No. 81072086) and Scientific and Technological Research Program of Chongqing Municipal Education Committee of China (Grant No. KJ110305).

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    Authors and Affiliations

    1. The Key Laboratory of Diagnostics Medicine designated by the Ministry of Education, Chongqing Medical University, No. 1 Yixueyuan Road, Yu Zhong District, Chongqing, People’s Republic of China

      Xue Yang, Liping Ou, Min Tang, Yin Wang, Xiaorong Wang, E Chen & Chunli Luo

    2. Department of Urinary Surgery, The First Affiliated Hospital of Chongqing Medical University, Chongqing, People’s Republic of China

      Jianjun Diao & Xiaohou Wu

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    1. Xue Yang
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    2. Liping Ou
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    3. Min Tang
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    Correspondence to Chunli Luo.

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    Xue Yang and Liping Ou contributed equally to this work.

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    Yang, X., Ou, L., Tang, M. et al. Knockdown of PLCε inhibits inflammatory cytokine release via STAT3 phosphorylation in human bladder cancer cells. Tumor Biol. 36, 9723–9732 (2015). https://doi.org/10.1007/s13277-015-3712-8

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    • DOI: https://doi.org/10.1007/s13277-015-3712-8

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