Synergistic effect of oridonin and a PI3K/mTOR inhibitor on the non-germinal center B cell-like subtype of diffuse large B cell lymphoma

Kai Qing; Zhen Jin; Wanbin Fu; Wenfang Wang; Zhao Liu; Xiaoyang Li; Zizhen Xu; Junmin Li

doi:10.1186/s13045-016-0303-0

Synergistic effect of oridonin and a PI3K/mTOR inhibitor on the non-germinal center B cell-like subtype of diffuse large B cell lymphoma

J Hematol Oncol. 2016 Aug 23;9(1):72. doi: 10.1186/s13045-016-0303-0.

Authors

Kai Qing¹, Zhen Jin¹, Wanbin Fu¹, Wenfang Wang¹, Zhao Liu², Xiaoyang Li², Zizhen Xu³, Junmin Li⁴

Affiliations

¹ Shanghai Institute of Hematology, State Key Laboratory for Medical Genomics, Ruijin Hospital affiliated to School of Medicine, Shanghai Jiao Tong University, Shanghai, China.
² Department of Hematology, Shanghai Institute of Hematology, Ruijin Hospital affiliated to School of Medicine, Shanghai Jiao Tong University, 197 Rui Jin Er Road, Shanghai, China.
³ Department of Laboratory Medicine, Ruijin Hospital affiliated to School of Medicine, Shanghai Jiao Tong University, 197 Rui Jin Er Road, Shanghai, China. [email protected].
⁴ Department of Hematology, Shanghai Institute of Hematology, Ruijin Hospital affiliated to School of Medicine, Shanghai Jiao Tong University, 197 Rui Jin Er Road, Shanghai, China. [email protected].

Abstract

We demonstrate the synergistic antitumor effect of oridonin and the PI3K/mTOR inhibitor NVP-BEZ235 on the non-germinal center B cell-like subtype of diffuse large B cell lymphoma (non-GCB DLBCL) both in vitro and in vivo. The underlying mechanism may be multifunctional, involving apoptosis, AKT/mTOR and NF-kB inactivation, and ROS-mediated DNA damage response. Our findings pave the way for a new potential treatment option for non-GCB DLBCL with the combination of oridonin and NVP-BEZ235.

Keywords: Apoptosis; Diffuse large B cell lymphoma; NF-kB; NVP-BEZ235; Oridonin; PI3K/mTOR.

Publication types

Letter

MeSH terms

Animals
Antineoplastic Combined Chemotherapy Protocols / therapeutic use
B-Lymphocytes / pathology
Cell Line, Tumor
Diterpenes, Kaurane / therapeutic use*
Drug Synergism
Heterografts
Humans
Imidazoles / therapeutic use*
Lymphoma, Large B-Cell, Diffuse / drug therapy*
Mice
Phosphatidylinositol 3-Kinases / metabolism
Protein Kinase Inhibitors / therapeutic use*
Quinolines / therapeutic use*
TOR Serine-Threonine Kinases / metabolism

Substances

Diterpenes, Kaurane
Imidazoles
Protein Kinase Inhibitors
Quinolines
oridonin
MTOR protein, human
TOR Serine-Threonine Kinases
dactolisib