TIPE attenuates the apoptotic effect of radiation and cisplatin and promotes tumor growth via JNK and p38 activation in Raw264.7 and EL4 cells

Liu,Yao; Ni,Xiao Yan; Chen,Rui Ling; Li,Juan; Gao,Feng Guang

doi:10.3892/or.2018.6351

TIPE attenuates the apoptotic effect of radiation and cisplatin and promotes tumor growth via JNK and p38 activation in Raw264.7 and EL4 cells

Authors:
- Yao Liu
- Xiao Yan Ni
- Rui Ling Chen
- Juan Li
- Feng Guang Gao
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Affiliations: Department of Immunology, Basic Medical Sciences, Medical College, Xiamen University, Xiamen, Fujian 361102, P.R. China
Published online on: April 3, 2018 https://doi.org/10.3892/or.2018.6351
Pages: 2688-2694

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Abstract

Tumor necrosis factor α‑induced protein 8 (TIPE) is highly expressed in many types of malignancies. Apoptosis is the process of programmed cell death which maintains the balance of cell survival and death. TIPE is involved in the carcinogenesis of many tumor types, yet the exact role of TIPE in defective apoptosis‑associated carcinogenesis remains uncertain. In the present study, TIPE‑overexpressing Raw264.7 and EL4 cells and vector control cells were treated with 4 mJ/cm2 ultraviolet radiation or 2 µg/ml cisplatin. Following ultraviolet irradiation, TIPE overexpression decreased the percentage of apoptotic cells as detected by flow cytometric and reversed the cisplatin‑mediated decrease in mitochondrial membrane potential by JC‑1 assay. Western blot analyses also revealed that TIPE overexpression inhibited cisplatin‑induced activation of caspase‑3 and ‑9 and PARP. Secondly, TIPE overexpression increased the levels of phosphorylated JNK, MEK and p38. Moreover, inhibition of JNK and p38, but not MEK, efficiently abolished the cell pro‑survival effect of TIPE. Most importantly, an in vivo tumor implantation model revealed that TIPE overexpression augmented the volume and weight of the implanted tumors, indicating that TIPE facilitated tumor formation. We found that TIPE exhibited an anti‑apoptotic effect via JNK and p38 activation, which ultimately promoted tumor. Hence, the present study revealed that activation of JNK and p38 kinases contribute to the TIPE‑mediated anti‑apoptotic effect, indicating that JNK and p38 may be potential therapeutic molecules for TIPE overexpression‑associated diseases.

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