Effects of Triptolide on Histone Acetylation and HDAC8 Expression in Multiple Myeloma in vitro

作     者：Fei Zhao Ling-lan Zeng Yan Chen Rui Li Yuan Liu Lu Wen Yi-quan Cheng Chun Zhang 

作者机构：Department of Hematology Union Hospital Tongji Medical College Huazhong University of Science and Technology Wuhan 430022 China 

出 版 物：《Chinese Journal of Cancer Research》 (中国癌症研究（英文版）)

年 卷 期：2010年第22卷第2期

页      面：148-155页

核心收录：

学科分类：1002[医学-临床医学] 100214[医学-肿瘤学] 10[医学] 

基　　金：supported by the National Natural Science Foundation of China(No.30700882) 

主　　题：Triptolide Histone acetylation HDAC8 Multiple myeloma 

摘      要：Objective： Multiple myeloma is a kind of malignant plasma cell disease that originated from B lymphocyte and secrete great amount of monoclonal immunoglobulin. It is still one of the refractory diseases at present. Numerous studies show that there is an intensive relationship between the disequilibrium of histone acetylation and the occurance of multiple myeloma. Here we investigated the effect of triptolide（TPL） on the proliferation, apoptosis, histone H3 and H4 acetylation and expression of histone deacetylase 8 （HDAC8） in vitro, to explore its anti- myeloma mechanism. Methods： The effect of triptolide on the growth of RPMI8226 was studied by 3-（4,5-Dimethyl-2-thiazolyl） -2,5-diphenyl-2H-tetrazolium（MTT） assay. Apoptosis was detected by Hoechst 33258 staining. The protein expressions of acetyl-histone H3 and H4 were determined by Western blot, and the expression of HDAC8 was assessed by RT-PCR, Western blot and confocal microscopy. Results： Triptolide inhibited the proliferation of RPMI8226 and induced apoptosis in a time- and dosedependent manner. The 36h IC50 value was （105.370 ± 0.189）nmol/L. Triptolide increased the acetylation of histone H3 and H4 greatly. Furthermore, triptolide significantly down-regulated the mRNA and protein expression of HDAC8. Conclusion： Triptolide can inhibit proliferation and induce apoptosis of RPMI8226 significantly. Triptolide reduces the expression of HDAC8 in order to increase the histone H3 and H4 acetylation, which is possibly the anti-myeloma mechanism of triptolide.