Proteasome inhibitors reduce CD73 expression partly via decreasing p-ERK in NSCLC cells
文献类型：期刊论文
| 作者 | Su, Ai-Ling2,3; Tian, Chang-Qing2,3; Ou, Ying-Jie2,3; Bao, Xu-Bin3; Huan, Xia-Juan3; Miao, Ze-Hong1,2,3; Wang, Ying-Qing1,2,3
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| 刊名 | LIFE SCIENCES
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| 出版日期 | 2023-11-01 |
| 卷号 | 332页码:10 |
| ISSN号 | 0024-3205 |
| 关键词 | CD73 Proteasome inhibitors ERK NSCLC |
| DOI | 10.1016/j.lfs.2023.122129 |
| 通讯作者 | Miao, Ze-Hong(zhmiao@simm.ac.cn) ; Wang, Ying-Qing(yqwang@simm.ac.cn) |
| 英文摘要 | Ecto-5'-nucleotidase (CD73), encoded by the NT5E gene, mediates tumor immunosuppression and has been targeted for the development of new anticancer drugs. Proteasome inhibitors impair protein degradation by inhibiting proteasome and have been used in the clinic for cancer therapy. Here we report that proteasome inhibitors reduce the protein and mRNA levels of CD73. Among 127 tested small-molecule drugs, proteasome inhibitors were found to consistently decrease the protein and mRNA levels of CD73 in NSCLC NCI-H1299 cells. This effect was further confirmed in different NSCLC cells exposed to different proteasome inhibitors. In those treated cells, the protein levels of ERK and its active form p-ERK, the vital components in the MAPK pathway, were reduced. Consistently, inhibitors of MEK and ERK, another two members of the MAPK pathway, also lowered the protein and mRNA levels of CD73. Correspondingly, treatments with fibroblast growth factor 2 (FGF2), an activator of the MAPK pathway, enhanced the levels of p-ERK and partly rescued the proteasome inhibitor-driven reduction of CD73 mRNA and protein in NSCLC cells. However, exogenous CD73 overexpression in murine Lewis lung carcinoma (LLC) cells was not lowered either in vitro or in vivo, by the treatments with proteasome inhibitors and basically, did not affect their in vitro proliferative inhibition either. In contrast, CD73 overexpression dramatically reduced the in vivo anticancer activity of Bortezomib in immunocompetent mice, with tumor growth inhibition rates from 52.18 % for LLC/vector down to 8.75 % for LLC/NT5E homografts. These findings give new insights into the anticancer mechanisms of proteasome inhibitors. |
| WOS关键词 | RAF/MEK/ERK PATHWAY ; ANTITUMOR-ACTIVITY ; BETA-CATENIN ; ADENOSINE ; TRANSCRIPTION ; BORTEZOMIB ; RESISTANCE ; ECTO-5'-NUCLEOTIDASE ; TARGET ; TUMOR |
| 资助项目 | Science and Technology Commission of Shanghai Municipality[20ZR1468100] ; National Natural Science Foundation of China[82073865] ; State Key Laboratory of Drug Research |
| WOS研究方向 | Research & Experimental Medicine ; Pharmacology & Pharmacy |
| 语种 | 英语 |
| 出版者 | PERGAMON-ELSEVIER SCIENCE LTD |
| WOS记录号 | WOS:001088582500001 |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/307578]  |
| 专题 | 新药研究国家重点实验室 |
| 通讯作者 | Miao, Ze-Hong; Wang, Ying-Qing |
| 作者单位 | 1.Shanghai Inst Mat Med, Canc Res Ctr, State Key Lab Drug Res, 501 Haike Rd, Shanghai 201203, Peoples R China 2.Univ Chinese Acad Sci, 19A Yuquan Rd, Beijing 100049, Peoples R China 3.Chinese Acad Sci, Canc Res Ctr, Shanghai Inst Mat Med, State Key Lab Drug Res, 501 Haike Rd, Shanghai 201203, Peoples R China |
| 推荐引用方式 GB/T 7714 | Su, Ai-Ling,Tian, Chang-Qing,Ou, Ying-Jie,et al. Proteasome inhibitors reduce CD73 expression partly via decreasing p-ERK in NSCLC cells[J]. LIFE SCIENCES,2023,332:10. |
| APA | Su, Ai-Ling.,Tian, Chang-Qing.,Ou, Ying-Jie.,Bao, Xu-Bin.,Huan, Xia-Juan.,...&Wang, Ying-Qing.(2023).Proteasome inhibitors reduce CD73 expression partly via decreasing p-ERK in NSCLC cells.LIFE SCIENCES,332,10. |
| MLA | Su, Ai-Ling,et al."Proteasome inhibitors reduce CD73 expression partly via decreasing p-ERK in NSCLC cells".LIFE SCIENCES 332(2023):10. |
入库方式： OAI收割
来源：上海药物研究所
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