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Acta Biochim Biophys Sin (Shanghai). 2018 Apr 1;50(4):399-407. doi: 10.1093/abbs/gmy021.

PKC inhibition of sotrastaurin has antitumor activity in diffuse large B-cell lymphoma via regulating the expression of MCT-1.

Chang G1,2, Zheng J3, Xiao W1,2, Chang S1,2, Wei Q3, Wu H1,2, Tao Y1,2, Yang G1,2, Xie B1,2, Lan X1,2, Wang Y1,2, Yu D1,2, Hu L1,2, Xie Y1,2, Bu W1,2, Kong Y1,2, Dai B4, Hou J1,2, Shi J1,2.

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Department of Hematology, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai 200072, China.
Tongji University Cancer Center, Tongji University, Shanghai 200072, China.
Department of Pathology, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai 200072, China.
College of Life Science and Technology, Tongji University, Shanghai 200092, China.


MCT-1 (multiple copies in T-cell lymphoma-1), a novel oncogene, was originally identified in T-cell lymphoma. A recent study has demonstrated that MCT-1 is highly expressed in 85% of diffuse large B-cell lymphomas (DLBCL). PKC (protein kinase C) plays an essential role in signal transduction for multiple biologically active substances for activating cellular functions and proliferation. In this study, we found that the mRNA and protein expression levels of MCT-1 were visibly decreased after knocking down PKC by siRNA in SUDHL-4 and OCI-LY8 DLBCL cell lines. A selective PKC inhibitor, sotrastaurin, effectively inhibited cell proliferation and induced cell apoptosis in a dose- and time-dependent manner. Meanwhile, we also observed that the cell cycle was arrested in the G1 phase in sotrastaurin-treated cells. In addition, MCT-1 was down-regulated in the sotrastaurin treatment group in vivo. Furthermore, we demonstrated that the PKC inhibitor sotrastaurin induced cell apoptosis and cell cycle arrest in DLBCL cells potentially through regulating the expression of MCT-1. Our data suggest that targeting PKC may be a potential therapeutic approach for lymphomas and related malignancies that exhibit high levels of MCT-1 protein.

[Indexed for MEDLINE]

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