Targeting SIRT1 to inhibit the proliferation of multiple myeloma cells

Lu,Bo; Zhang,Dengyang; Wang,Xiaobo; Lin,Dongjun; Chen,Yun; Xu,Xiaojun

doi:10.3892/ol.2021.12567

Targeting SIRT1 to inhibit the proliferation of multiple myeloma cells

Authors:
- Bo Lu
- Dengyang Zhang
- Xiaobo Wang
- Dongjun Lin
- Yun Chen
- Xiaojun Xu
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Affiliations: Department of Hematology, The Seventh Affiliated Hospital, Sun Yat‑Sen University, Shenzhen, Guangdong 518107, P.R. China
Published online on: February 21, 2021 https://doi.org/10.3892/ol.2021.12567
Article Number: 306
Copyright: © Lu et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Multiple myeloma (MM) is the second most common hematopoietic malignancy and remains an incurable disease. Thus, novel drugs and therapeutic methods are required for patients with MM. The present study aimed to investigate the effect of sirtuin 1 (SIRT1) inhibitor cambinol on the proliferation and apoptosis of myeloma cell lines, RPMI8226 and U266. Moreover, the present study evaluated the underlying molecular mechanisms of proliferation inhibition and apoptosis induced by cambinol. A Cell Counting Kit‑8 assay was used to measure the viability of RPMI8226 and U266 cells treated with cambinol. Apoptosis and the cell cycle were analyzed via flow cytometry. The expression levels of caspase‑3, poly(ADP‑ribose) polymerase 1 (PARP), p53, acetylated p53 (Ac‑p53), Bcl‑2, cyclin D1 and p21 were detected in cells treated with cambinol using western blot analysis. The results demonstrated that cambinol inhibited the proliferation of RPMI8226 and U266 cells in a time‑ and dose‑dependent manner. Increased apoptosis and G1 cell cycle arrest, together with enhanced procaspase‑3 degradation and PARP cleavage were identified in cambinol‑treated cells compared with controls. Western blotting results also revealed the upregulation of p53 acetylation and p21, as well as the downregulation of Bcl‑2 and cyclin D1 in cells treated with cambinol. In conclusion, the present results suggest that cambinol inhibits the proliferation and induces apoptosis in RPMI8226 and U266 cells by regulating acetylation of p53 via the targeting of SIRT1.

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