Lactate Decreases Bortezomib Sensitivity and Predicts Poor Clinical Outcomes of Multiple Myeloma.

Autor: Ma NY; Medical Center of Hematology, Xinqiao Hospital, Army Medical University, Chongqing, 400037, China.; State Key Laboratory of Trauma, Burns and Combined Injury, Army Medical University, Chongqing, 400037, China., Li Q; Medical Center of Hematology, Xinqiao Hospital, Army Medical University, Chongqing, 400037, China.; State Key Laboratory of Trauma, Burns and Combined Injury, Army Medical University, Chongqing, 400037, China., Li XL; Medical Center of Hematology, Xinqiao Hospital, Army Medical University, Chongqing, 400037, China.; State Key Laboratory of Trauma, Burns and Combined Injury, Army Medical University, Chongqing, 400037, China., Zeng YJ; Medical Center of Hematology, Xinqiao Hospital, Army Medical University, Chongqing, 400037, China.; State Key Laboratory of Trauma, Burns and Combined Injury, Army Medical University, Chongqing, 400037, China., Huang DZ; Medical Center of Hematology, Xinqiao Hospital, Army Medical University, Chongqing, 400037, China.; State Key Laboratory of Trauma, Burns and Combined Injury, Army Medical University, Chongqing, 400037, China., Duan YS; Medical Center of Hematology, Xinqiao Hospital, Army Medical University, Chongqing, 400037, China.; State Key Laboratory of Trauma, Burns and Combined Injury, Army Medical University, Chongqing, 400037, China., Xia J; Medical Center of Hematology, Xinqiao Hospital, Army Medical University, Chongqing, 400037, China.; State Key Laboratory of Trauma, Burns and Combined Injury, Army Medical University, Chongqing, 400037, China., Liu BD; Medical Center of Hematology, Xinqiao Hospital, Army Medical University, Chongqing, 400037, China.; State Key Laboratory of Trauma, Burns and Combined Injury, Army Medical University, Chongqing, 400037, China., Rao LY; Medical Center of Hematology, Xinqiao Hospital, Army Medical University, Chongqing, 400037, China.; State Key Laboratory of Trauma, Burns and Combined Injury, Army Medical University, Chongqing, 400037, China., Rao J; Medical Center of Hematology, Xinqiao Hospital, Army Medical University, Chongqing, 400037, China. raojun1129@126.com.; State Key Laboratory of Trauma, Burns and Combined Injury, Army Medical University, Chongqing, 400037, China. raojun1129@126.com.; National Clinical Research Center for Hematologic Diseases, First Affiliated Hospital of Soochow University, Soochow, 215031, China. raojun1129@126.com., Zhang X; Medical Center of Hematology, Xinqiao Hospital, Army Medical University, Chongqing, 400037, China. zhangxxi@sina.com.; State Key Laboratory of Trauma, Burns and Combined Injury, Army Medical University, Chongqing, 400037, China. zhangxxi@sina.com.; National Clinical Research Center for Hematologic Diseases, First Affiliated Hospital of Soochow University, Soochow, 215031, China. zhangxxi@sina.com.
Jazyk: angličtina
Zdroj: Current medical science [Curr Med Sci] 2023 Aug; Vol. 43 (4), pp. 679-688. Date of Electronic Publication: 2023 Jun 16.
DOI: 10.1007/s11596-023-2747-0
Abstrakt: Objective: Metabolic disorders are regarded as hallmarks of multiple myeloma (MM) and are responsible for rapid cancer cell proliferation and tumor growth. However, the exact biological roles of metabolites in MM cells have not been fully explored. This study aimed to explore the feasibility and clinical significance of lactate for MM and investigate the molecular mechanism of lactic acid (Lac) in the proliferation of myeloma cells and cell sensitivity to bortezomib (BTZ).
Methods: Metabolomic analysis of the serum was carried out to obtain metabolites expression and clinical characteristics in MM patients. The CCK8 assay and flow cytometry were used to detect cell proliferation, apoptosis, and cell cycle changes. Western blotting was used to detect the potential mechanism and apoptosis- and cycle-related protein changes.
Results: Lactate was highly expressed in both the peripheral blood and bone marrow of MM patients. It was significantly correlated with Durie-Salmon Staging (DS Staging) and the International Staging System (ISS Staging) and the serum and urinary involved/uninvolved free light chain ratios. Patients with relatively high lactate levels had a poor treatment response. Moreover, in vitro experiments showed that Lac could promote the proliferation of tumor cells and decrease the proportion of G0/G1-phase cells, which was accompanied by an increased proportion of S-phase cells. In addition, Lac could decrease tumor sensitivity to BTZ by disrupting the expression of nuclear factor kappa B subunit 2 (NFkB2) and RelB.
Conclusion: Metabolic changes are important in MM cell proliferation and treatment response; lactate could be used as a biomarker in MM and as a therapeutic target to overcome cell resistance to BTZ.
(© 2023. Huazhong University of Science and Technology.)
Databáze: MEDLINE
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