Tropical Journal of Pharmaceutical Research

Original Research Article | OPEN ACCESS

Resveratrol increases the sensitivity of multiple myeloma cells against bortezomib via Hedgehog signaling pathway

Riyong Zhou¹, Ruye Ma², Zhenlin Jin³, Liyuan Tang³, Ying Zhou⁴, Yu Zhang³

¹Department of Anesthesiology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang 325015; ²Department of Hematology, Jinshan Hospital of Fudan University, Jinan, Shandong 201500; ³Department of Hematology, The First Affiliated Hospital of Wenzhou Medical UniversityA292;WenzhouA292;Zhejiang, 325015; ⁴Department of Nephrology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang 325015, China.

For correspondence:- Yu Zhang Email: YuZhangsdf@163.com Tel:+8657755579481

Accepted: 29 September 2019 Published: 31 October 2019

Citation: Zhou R, Ma R, Jin Z, Tang L, Zhou Y, Zhang Y. Resveratrol increases the sensitivity of multiple myeloma cells against bortezomib via Hedgehog signaling pathway. Trop J Pharm Res 2019; 18(10):2133-2138 doi: 10.4314/tjpr.v18i10.19

© 2019 The authors.
This is an Open Access article that uses a funding model which does not charge readers or their institutions for access and distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0) and the Budapest Open Access Initiative (http://www.budapestopenaccessinitiative.org/read), which permit unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited..

Abstract

Purpose: To investigate the effect of resveratrol (RSV) on bortezomib (BTZ)-resistant multiple myeloma (MM) cells, and to elucidate the underlying mechanism of action.

Methods: H929 cell lines were exposed to BTZ for 8 months to establish BTZ-resistant MM cell model. Cell proliferation was determined by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Apoptosis was measured using annexin V/propidium iodide (PI) staining while cell cycle analysis was evaluated by flow cytometry. The expression of Hedgehog (Hh) signaling proteins (sonic hedgehog (SHH), smoothened (SMO), and glioma-associated oncogene homolog (GLI)) was analyzed by western blot.

Results: H929R was confirmed as a MM cell line that is resistant to BTZ. RSV enhanced the sensitivity of H929R cells against BTZ via inhibition of cell viability and colony formation, induction of cell apoptosis and regulation of expression of apoptosis-related proteins. Furthermore, RSV inhibited the expression of Hh signaling proteins (p < 0.05.

Conclusion: RSV enhances the sensitivity of MM cells to BTZ, partly via Hh signaling pathway. Thus, Hh pathway is a probable target for MM treatment, and RSV has potentials for use in the clinical management of MM.

Keywords: Resveratrol, Bortezomib, Hedgehog signaling pathway, Multiple myeloma