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ECPIRM, a Potential Therapeutic Agent for Cutaneous T-Cell Lymphoma, Inhibits Cell Proliferation and Promotes Apoptosis via a JAK/STAT Pathway

[ Vol. 18 , Issue. 3 ]

Author(s):

Hua Yang, Pengcheng Ma*, Yuping Cao, Mengli Zhang, Lingjun Li, Jun Wei, Lei Tao and Kun Qian   Pages 401 - 411 ( 11 )

Abstract:


Background: Retinoids are important agents for the treatment of cutaneous T-cell lymphomas (CTCL). But side effects and drug resistance caused by activation of RAR/RXR limited their clinical application. Therefore, it is urgent to develop new agents to fight against CTCL. ECPIRM, a 13-cis retinoic acid derivative, was reported that it inhibited proliferation and induced apoptosis of SCL-1 cells.

Objective: The aim of this study was to evaluate the biological activities and mechanisms of ECPIEM.

Methods: The effect of ECPIRM on cell proliferation was determined by MTT assay and Trypan blue exclusion assay while FACS analysis was used to detect changes in cell cycle and apoptosis in HUT78 cells. The influence of ECPIRM on RAR/RXR and JAK/STAT signaling was evaluated by western blot analysis.

Results: ECPIRM, better than other agents (all-trans retinoic acid,13-cis-retinoic acid or bexarotene), inhibited proliferation and induced apoptosis significantly in HUT78 cells, but with little cytotoxicity on normal lymphocytes. Then ECPIRM induced G0/G1 phase arrest by decreasing the expression of cyclinD1, cyclinE, CDK2 and CDK4 while increasing p21. Furthermore, the unaffected expression of RAR and RXR members suggested that ECPIRM acted independently of RAR/RXR pathway in HUT78 cells. But decreased phosphorylation of JAK1, STAT3, STAT5 and downregulated Bcl-xL, Cyclin D1 and c-Myc indicated that ECPIRM inhibited the activation of JAK/STAT signaling.

Conclusion: ECPIRM inhibited proliferation, induced apoptosis and G0/G1 phase arrest in HUT78 cells through inhibiting JAK/STAT pathway but not RAR/RXR pathway, which presented ECPIRM as a promising candidate for the treatment of CTCL patients.

Keywords:

Cutaneous T-cell lymphomas, Retinoids, ECPIRM, RAR, RXR, JAK/STAT pathway.

Affiliation:

Institute of Dermatology, Chinese Academy of Medical Sciences, Peking Union Medical College, Jiangwangmiao Street, Nanjing 210042, Institute of Dermatology, Chinese Academy of Medical Sciences, Peking Union Medical College, Jiangwangmiao Street, Nanjing 210042, Institute of Dermatology, Chinese Academy of Medical Sciences, Peking Union Medical College, Jiangwangmiao Street, Nanjing 210042, Institute of Dermatology, Chinese Academy of Medical Sciences, Peking Union Medical College, Jiangwangmiao Street, Nanjing 210042, Institute of Dermatology, Chinese Academy of Medical Sciences, Peking Union Medical College, Jiangwangmiao Street, Nanjing 210042, Institute of Dermatology, Chinese Academy of Medical Sciences, Peking Union Medical College, Jiangwangmiao Street, Nanjing 210042, Institute of Dermatology, Chinese Academy of Medical Sciences, Peking Union Medical College, Jiangwangmiao Street, Nanjing 210042, Institute of Dermatology, Chinese Academy of Medical Sciences, Peking Union Medical College, Jiangwangmiao Street, Nanjing 210042

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