Antitumor effects of rafoxanide in diffuse large B cell lymphoma via the PTEN/PI3K/Akt and JNK/c-Jun pathways

doi:10.1016/j.lfs.2019.117249

	Antitumor effects of rafoxanide in diffuse large B cell lymphoma via the PTEN/PI3K/Akt and JNK/c-Jun pathways
	He, Wan 1; Xu, Zhijian 2; Song, Dongliang 1; Zhang, Hui 1; Li, Bo 2; Gao, Lu 1; Zhang, Yong 2; Feng, Qilin 1; Yu, Dandan 1; Hu, Liangning 1
刊名	LIFE SCIENCES
	2020-02-15
卷号	243 页码:11
关键词	Diffuse large B-cell lymphoma Rafoxanide PTEN/PI3K/AKT Apoptosis DNA damage
ISSN号	0024-3205
DOI	10.1016/j.lfs.2019.117249
通讯作者	Shi, Jumei(shijumei@tongji.edu.cn) ; Zhu, Weiliang(wlzhu@simm.ac.cn)
英文摘要	Aims: Diffuse large B-cell lymphoma (DLBCL) is one of the most aggressive lymphoid malignancies, which remains incurable, thus warranting the development of new therapies. Our previous study determined that rafoxanide is very effective in treating multiple myeloma (MM). In the present study, we tried to evaluate the effects of rafoxanide on DLBCL, as well as the potential underlying molecular mechanisms. Main methods: We used CCK-8 assay and flow cytometry to assess cell viability and apoptosis. The proteins and pathways associated with apoptosis and proliferation were evaluated through western blot, and xenograft mice were used as the experimental animal model. We also used the TUNEL assay and immunofluorescence for further analyses. Key findings: Treatment with different doses of rafoxanide significantly inhibited cell viability and apoptosis. Additionally, the compound induced cell cycle arrest, reduced mitochondrial membrane potential (Delta psi m), and stimulated reactive oxygen species (ROS) generation without the influence of normal peripheral blood monocytes (PBMCs). As expected, rafoxanide played a role in regulating these proteins and the PTEN/PI3K/AKT and JNK/c-Jun pathways. Furthermore, immunofluorescence and western blot results showed that rafoxanide up-regulated H2AX phosphorylation and then inhibited DNA repair in DLBCL. In the xenograft mouse model, tumor volumes were reduced after intraperitoneal injection with rafoxanide. We also observed that TUNEL positive cells were remarkably increased in rafoxanide-treated tumor tissues. Significance: These results collectively provide a novel choice to regular treatment for DLBCL patients with poor prognosis.
资助项目	National Natural Science Foundation of China[81529001] ; National Natural Science Foundation of China[81670194,81870158] ; National Natural Science Foundation of China[81570190] ; National Science & Technology Major Project Key New Drug Creation and Manufacturing Program, China[2018ZX09711002]
WOS关键词	TERMINAL KINASE JNK ; DNA-DAMAGE ; ACTIVATION ; INHIBITORS ; OUTCOMES ; CANCER ; CYCLE
WOS研究方向	Research & Experimental Medicine ; Pharmacology & Pharmacy
语种	英语
出版者	PERGAMON-ELSEVIER SCIENCE LTD
WOS记录号	WOS:000512996200009
内容类型	期刊论文
源URL	[http://119.78.100.183/handle/2S10ELR8/281247]
专题	中国科学院上海药物研究所
通讯作者	Shi, Jumei; Zhu, Weiliang
作者单位	1.Tongji Univ, Shanghai Peoples Hosp 10, Dept Hematol, Sch Med, 301 Yanchang Rd, Shanghai 200072, Peoples R China 2.Chinese Acad Sci, Drug Discovery & Design Ctr, Shanghai Inst Mat Med, CAS Key Lab Receptor Res, 555 Zuchongzhi Rd, Shanghai 201203, Peoples R China
推荐引用方式 GB/T 7714	He, Wan,Xu, Zhijian,Song, Dongliang,et al. Antitumor effects of rafoxanide in diffuse large B cell lymphoma via the PTEN/PI3K/Akt and JNK/c-Jun pathways[J]. LIFE SCIENCES,2020,243:11.
APA	He, Wan.,Xu, Zhijian.,Song, Dongliang.,Zhang, Hui.,Li, Bo.,...&Zhu, Weiliang.(2020).Antitumor effects of rafoxanide in diffuse large B cell lymphoma via the PTEN/PI3K/Akt and JNK/c-Jun pathways.LIFE SCIENCES,243,11.
MLA	He, Wan,et al."Antitumor effects of rafoxanide in diffuse large B cell lymphoma via the PTEN/PI3K/Akt and JNK/c-Jun pathways".LIFE SCIENCES 243(2020):11.