Triptolide enhances the sensitivity of multiple myeloma cells to dexamethasone via microRNAs

被引:26
作者
Huang, Xin [1 ,2 ,3 ]
Yang, Min [1 ]
Jin, Jie [1 ,2 ,3 ]
机构
[1] Zhejiang Univ, Sch Med, Affiliated Hosp 1, Dept Hematol, Hangzhou 310003, Zhejiang, Peoples R China
[2] Zhejiang Univ, Inst Hematol, Hangzhou 310003, Zhejiang, Peoples R China
[3] Key Lab Hematol Diag & Treatment, Hangzhou, Zhejiang, Peoples R China
基金
中国国家自然科学基金;
关键词
Triptolide; multiple myeloma; glucocorticoid receptor microRNAs; TRIPTERYGIUM-WILFORDII HOOK; GLUCOCORTICOID-RECEPTOR; INDUCED APOPTOSIS; EXPRESSION; INDUCTION; GROWTH; ACTIVATION; INHIBITION; RESISTANCE; THERAPY;
D O I
10.3109/10428194.2011.638069
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Recently triptolide (TPL) has been proved to have the capacity to inhibit the proliferation of multiple myeloma (MM) cells as well as leukemic cells in vitro. In the present study, we found a synergistic effect when TPL was added to dexamethasone to induce apoptosis in MM.1S cells. This combination induced a significantly higher proportion of apoptotic cells compared with those treated with each drug separately. TPL down-regulated the expression of miR142-5p and miR181a, which have been shown to inhibit glucocorticoid receptor (GR) expression. MicroRNA mimics and inhibitors inhibited or enhanced the synergistic effect between TPL and dexamethasone in inducing apoptosis in MM.1S cells, suggesting an important role of miR142-5p and miR181a in GR regulation by TPL. The in vitro proapoptotic effect of TPL associated with dexamethasone reveals a new lead for further clinical investigation into the treatment of patients with MM with TPL.
引用
收藏
页码:1188 / 1195
页数:8
相关论文
共 40 条
[1]   Multiple myeloma [J].
Bataille, R ;
Harousseau, JL .
NEW ENGLAND JOURNAL OF MEDICINE, 1997, 336 (23) :1657-1664
[2]   Triptolide sensitizes AML cells to TRAIL-induced apoptosis via decrease of XIAP and p53-mediated increase of DR5 [J].
Carter, Bing Z. ;
Mak, Duncan H. ;
Schober, Wendy D. ;
Dietrich, Martin F. ;
Pinilla, Clernencia ;
VassileV, Lyubornir T. ;
Reed, John C. ;
Andreeff, Michael .
BLOOD, 2008, 111 (07) :3742-3750
[3]   Tliptolide induces caspase-dependent cell death mediated via the mitochondfial pathway in leukemic cells [J].
Carter, Bing Z. ;
Mak, Duncan H. ;
Schober, Wendy D. ;
McQueen, Teresa ;
Harris, David ;
Estrov, Zeev ;
Evans, Randall L. ;
Andreeff, Michael .
BLOOD, 2006, 108 (02) :630-637
[4]   Triptolide and chemotherapy cooperate in tumor cell apoptosis - A role for the p53 pathway [J].
Chang, WT ;
Kang, JJ ;
Lee, KY ;
Wei, K ;
Anderson, E ;
Gotmare, S ;
Ross, JA ;
Rosen, GD .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2001, 276 (03) :2221-2227
[5]   Triptolide, a novel immunosuppressive and anti-inflammatory agent purified from a Chinese herb Tripterygium Wilfordii Hook F [J].
Chen, BJ .
LEUKEMIA & LYMPHOMA, 2001, 42 (03) :253-265
[6]   Genetic events in the pathogenesis of multiple myeloma [J].
Chng, W. J. ;
Glebov, O. ;
Bergsagel, R. L. ;
Kuehl, W. M. .
BEST PRACTICE & RESEARCH CLINICAL HAEMATOLOGY, 2007, 20 (04) :571-596
[7]   Immunosuppressant PG490 (triptolide) induces apoptosis through the activation of caspase-3 and down-regulation of XIAP in U937 cells [J].
Choi, YJ ;
Kim, TG ;
Kim, YH ;
Lee, SH ;
Kwon, YK ;
Suh, SI ;
Park, JW ;
Kwon, TK .
BIOCHEMICAL PHARMACOLOGY, 2003, 66 (02) :273-280
[8]   Molecular understanding and modern application of traditional medicines: Triumphs and trials [J].
Corson, Timothy W. ;
Crews, Craig M. .
CELL, 2007, 130 (05) :769-774
[9]   From traditional Chinese medicine to rational cancer therapy [J].
Efferth, Thomas ;
Li, Paul C. H. ;
Konkimalla, Venkata S. Badireenath ;
Kaina, Bernd .
TRENDS IN MOLECULAR MEDICINE, 2007, 13 (08) :353-361
[10]   PG490-mediated sensitization of lung cancer cells to Apo2L/TRAIL-induced apoptosis requires activation of ERK2 [J].
Frese, S ;
Pirnia, F ;
Miescher, D ;
Krajewski, S ;
Borner, MM ;
Reed, JC ;
Schmid, RA .
ONCOGENE, 2003, 22 (35) :5427-5435