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03 May 2018 : Laboratory Research  

Interleukin-22 (IL-22) Regulates Apoptosis of Paclitaxel-Resistant Non-Small Cell Lung Cancer Cells Through C-Jun N-Terminal Kinase Signaling Pathway

Chenchen Li1ABCDEFG, Xia Zhao2ABCDEFG, Yang Yang1BCDEF, Siwen Liu1CDEF, Yun Liu1DEF, Xiaoyou Li1ABCDEFG*

DOI: 10.12659/MSM.907336

Med Sci Monit 2018; 24: LBR2750-2757

Abstract

BACKGROUND: Reducing drug resistance in tumor cells has become an important issue for cancer treatment. The purpose of this study was to investigate whether IL-22 was involved in lung cancer cell resistance to paclitaxel (PTX), and to explore the underlying molecular mechanism.

MATERIAL AND METHODS: Non-small cell lung cancer (NSCLC) cell line A549 and the drug resistant cell line A549/PTX were used in the present study. The inhibitory rate of PTX on A549 and A549/PTX cell proliferation was determined by MTT assay and the half-maximal inhibitory concentration (IC50) value was calculated. The expression level of IL-22 was detected using Western blot and qRT-PCR. To elucidate the mechanism by which IL-22 is involved in PTX resistance, a stable IL-22-silenced A549/PTX cell line was generated by using IL-22-siRNA. Cell apoptosis was analyzed by flow cytometry, and the c-Jun N-terminal kinase (JNK) signal pathway was determined using Western blot analysis.

RESULTS: We found that IL-22 expression level was markedly higher in A549/PTX cells than in A549 cells, and IL-22 gene knockdown significantly enhanced the cell proliferation inhibition rate of PTX to A549/PTX cells and decreased the IC50 value of PTX to A549/PTX cells, indicating IL-22 was involved in cell PTX resistance. Our findings also suggest that IL-22 knockdown notably increased PTX induced apoptosis in A549/PTX cells. Moreover, the results showed that p-JNK and Caspase 3 expression were significantly increased in IL-22 knockdown A549/PTX cells, while Bcl-2 expression was significantly decreased.

CONCLUSIONS: IL-22 is involved in A549 cell resistance to PTX through regulating cell apoptosis via the JNK signaling pathway.

Keywords: Drug Resistance, paclitaxel

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Medical Science Monitor eISSN: 1643-3750
Medical Science Monitor eISSN: 1643-3750