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Chenchen Li, Xia Zhao, Yang Yang, Siwen Liu, Yun Liu, Xiaoyou Li
(Department of Medical Oncology, Jiangsu Cancer Hospital, Jiangsu Institute of Cancer Research, Nanjing Medical University Affiliated Cancer Hospital, Nanjing, Jiangsu, China (mainland))
Med Sci Monit 2018; 24:2750-2757
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.