[Cdc37 Contributes to bortezomib resistance in multiple myeloma via autophagy].

Autor:	Liu LT; State Key Laboratory of Experimental Hematology, National Clinical Research Center for Blood Diseases, Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin 300020, China., Deng SH; State Key Laboratory of Experimental Hematology, National Clinical Research Center for Blood Diseases, Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin 300020, China., Zang MR; Department of Hematology, The Third Affiliated Hospital of Hebei Medical University, Shijiazhuang 050000, China., Zhang JQ; Department of Hematology, The Third Affiliated Hospital of Hebei Medical University, Shijiazhuang 050000, China., Qiu LG; State Key Laboratory of Experimental Hematology, National Clinical Research Center for Blood Diseases, Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin 300020, China.
Jazyk:	čínština
Zdroj:	Zhonghua xue ye xue za zhi = Zhonghua xueyexue zazhi [Zhonghua Xue Ye Xue Za Zhi] 2020 Jul 14; Vol. 41 (7), pp. 583-588.
DOI:	10.3760/cma.j.issn.0253-2727.2020.07.009
Abstrakt:	Objective: To explore the role of cell division cycle protein 37 (Cdc37) mediating bortezomib (BTZ) resistance in multiple myeloma (MM) via the regulation of autophagy activity to provide a novel strategy for MM therapy. Methods: The expressions of Cdc37 and LC3b were investigated in BTZ-resistant MM cell line ANBL-6.BR using quantitative real-time PCR (qRT-PCR) and western blot (WB) analysis. Cdc37 was upregulated in ANBL-6.BR cells owing to lentivirus transfection. The LC3b expression was detected with WB, and BTZ-induced apoptosis was explored using flow cytometry. Cdc37 was then down-regulated by shRNA in the MM cell line NCI-H929. Sensitivity of BTZ was evaluated using CCK-8 analysis. WB analysis was performed to check the expression of the AKT/mTOR pathway and autophagy-associated proteins. The sensitivity of NCI-H929 cells to BTZ in the presence of autophagy inhibitor chloroquine (CQ) was analyzed using flow cytometry. Results: Cdc37 was down-regulated, while autophagy-associated gene LC3b was upregulated in BTZ-resistant cell line ANBL-6.BR. Up-regulated Cdc37 in ANBL-6.BR cells could inhibit LC3b expression and increase the sensitivity of MM to BTZ. Suppressing Cdc37 expression in MM cell line NCI-H929 induced BTZ resistance and autophagy activation, while CQ could rescue BTZ resistance caused by Cdc37 inhibition. Conclusion: Cdc37 may participate in BTZ resistance in MM via the regulation of autophagy activity.
Databáze:	MEDLINE
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