Thoracic Cardiovascular Surgery, Inner Mongolia Forestry General Hospital, Yakeshi, 022150, China.
The Sixth Hospital of Wuhan, Affiliated Hospital of Jianghan University, No. 168 Hong Kong Road, Jiang'an District, Wuhan, 430015, Hubei Province, China.
Hum Cell. 2020 Jul;33(3):850-858. doi: 10.1007/s13577-020-00373-3. Epub 2020 May 25.
The chemoresistance of tumors is the main barrier to cancer treatment. Interleukin-22 (IL-22) plays an important role in the chemoresistance of multi-cancers; however, the roles of IL-22 in the paclitaxel resistance of lung adenocarcinoma cells remain to be investigated. The present study aims to investigate the potential mechanisms of IL-22 enhancing the chemoresistance of lung adenocarcinoma cells to paclitaxel. We cultured A549, H358, and A549/PTX cell lines. qRT-PCR and western blot assays were performed to examine the mRNA and/or protein levels of IL-22 in A549, A549/PTX, H358, and H358/PTX. Moreover, cells were transfected with IL-22 siRNA1, IL-22 siRNA2, and siRNA NC, and treated with paclitaxel, and the proliferation rate of lung adenocarcinoma cells was evaluated by MTT assay. Flow cytometry was conducted to determine the apoptosis rate of lung adenocarcinoma cells. The results showed that the expression of IL-22 in lung adenocarcinoma tissues was higher than that in normal tissues, and the expression of IL-22 was higher in A549/PTX and H358/PTX compared with A549 and H358 cells. Meanwhile, the expression of IL-22 was strongly correlated with smoking history and TMN stage, as well. Furthermore, IL-22 siRNA inhibited the proliferation and promoted the apoptosis of A549/PTX and H358/PTX cells, and IL-22 siRNA also suppressed the expression levels of AKT and Bcl-2 and increased the expression levels of Bax and cleaved caspase 3. To sum up, IL-22 may mediate the chemosensitivity of lung adenocarcinoma cells to paclitaxel through inhibiting the AKT signaling pathways.
肿瘤的化疗耐药性是癌症治疗的主要障碍。白细胞介素-22(IL-22)在多种癌症的化疗耐药性中发挥重要作用;然而,IL-22 在肺腺癌细胞紫杉醇耐药中的作用仍有待研究。本研究旨在探讨 IL-22 增强肺腺癌细胞对紫杉醇化疗耐药性的潜在机制。我们培养了 A549、H358 和 A549/PTX 细胞系。通过 qRT-PCR 和 Western blot 检测 A549、A549/PTX、H358 和 H358/PTX 中 IL-22 的 mRNA 和/或蛋白水平。此外,用 IL-22 siRNA1、IL-22 siRNA2 和 siRNA NC 转染细胞,并用紫杉醇处理,通过 MTT 测定评估肺腺癌细胞的增殖率。通过流式细胞术测定肺腺癌细胞的凋亡率。结果显示,肺腺癌组织中 IL-22 的表达高于正常组织,A549/PTX 和 H358/PTX 中的 IL-22 表达高于 A549 和 H358 细胞。同时,IL-22 的表达与吸烟史和 TMN 分期密切相关。此外,IL-22 siRNA 抑制 A549/PTX 和 H358/PTX 细胞的增殖并促进其凋亡,并且 IL-22 siRNA 还抑制 AKT 和 Bcl-2 的表达水平并增加 Bax 和 cleaved caspase 3 的表达水平。总之,IL-22 可能通过抑制 AKT 信号通路介导肺腺癌细胞对紫杉醇的化疗敏感性。