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A novel stealth liposomal topotecan with amlodipine: Apoptotic effect is associated with deletion of intracellular Ca2+ by amlodipine thus leading to an enhanced antitumor activity in leukemia
Li, X; Ruan, GR; Lu, WL; Hong, HY; Liang, GW; Zhang, YT; Liu, Y; Long, C; Ma, X; Yuan, L; Wang, JC; Zhang, X; Zhang, Q
关键词Stealth Liposomal Topotecan With Amlodipine Caspases Intracellular Calcium Ion Signaling Pathway Leukemia
刊名JOURNAL OF CONTROLLED RELEASE
2006-05-15
DOI10.1016/j.jconrel.2006.01.007
112期:2页:186-198
收录类别SCI
文章类型Article
WOS标题词Science & Technology
类目[WOS]Chemistry, Multidisciplinary ; Pharmacology & Pharmacy
研究领域[WOS]Chemistry ; Pharmacology & Pharmacy
关键词[WOS]CELL LUNG-CANCER ; CARCINOMA A431 CELLS ; IN-VITRO ; OVARIAN-CANCER ; BREAST-CANCER ; RESISTANCE PROTEIN ; PHASE-I ; DOXORUBICIN ; GROWTH ; MICE
英文摘要

The objectives of the present study were to define whether amlodipine induces apoptosis and what mechanism is involved in the process in human resistant and non-resistant leukemia cells following co-administration of stealth liposomal topotecan with amlodipine, a novel antiresistant liposomes developed by our institution. In three leukemias, K562, HL-60, and multidrug resistant (MDR) HL-60, cytotoxicity of topotecan was potentiated by amolodipne, while topotecan alone was resistant to MDR HL-60 cells. In two selected K562 or MDR HL-60 cells, the apoptotic effects were increased by addition of amlodipme, showing a dose-dependent manner. The activities of caspase 3 and 7 (marked as caspase 3/7), and caspase 8 were significantly activated by topotecan with amlodipme co-treated as the stealth liposomes. The deletions of intracellular Ca2+ stores induced by amlodipine correlated with the activated activities of caspase 3/7, or 8, respectively. In xenograft model with MDR HL-60 in nude mice, antitumor activity of stealth liposomal topotecan with amlodipine was significantly enhanced as compared to that of stealth liposomal topotecan or topotecan alone. In conclusion, apoptotic effect is associated with deletion of intracellular Ca2+ by amlodipine through activation of caspase 8 and then 3/7 activities. The enhanced antitumor activities by stealth liposomal topotecan with amlodipine are mainly due to the potentiating apoptotic effect and reversing the resistance by amlodipine. Stealth liposomal encapsulation of anticancer agent with a modulator may provide a novel strategy for improving the chemotherapeutic effects. (c) 2006 Elsevier B.V. All rights reserved.

语种英语
WOS记录号WOS:000237908100005
引用统计
被引频次:42[WOS]   [WOS记录]     [WOS相关记录]
文献类型期刊论文
条目标识符http://ir.bjmu.edu.cn/handle/400002259/55983
专题北京大学药学院_药剂学系
作者单位1.Peking Univ, Peoples Hosp, Beijing 100083, Peoples R China
2.Peking Univ, Inst Hematol, Beijing 100083, Peoples R China
3.Peking Univ, Sch Pharmaceut Sci, Dept Pharmaceut, Beijing 100083, Peoples R China
4.Beijing Med Univ, United Biol Engn Co, Beijing 100083, Peoples R China
5.Peking Univ, Ctr Human Dis Genom, Beijing 100083, Peoples R China
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Li, X,Ruan, GR,Lu, WL,et al. A novel stealth liposomal topotecan with amlodipine: Apoptotic effect is associated with deletion of intracellular Ca2+ by amlodipine thus leading to an enhanced antitumor activity in leukemia[J]. JOURNAL OF CONTROLLED RELEASE,2006,112(2):186-198.
APA Li, X.,Ruan, GR.,Lu, WL.,Hong, HY.,Liang, GW.,...&Zhang, Q.(2006).A novel stealth liposomal topotecan with amlodipine: Apoptotic effect is associated with deletion of intracellular Ca2+ by amlodipine thus leading to an enhanced antitumor activity in leukemia.JOURNAL OF CONTROLLED RELEASE,112(2),186-198.
MLA Li, X,et al."A novel stealth liposomal topotecan with amlodipine: Apoptotic effect is associated with deletion of intracellular Ca2+ by amlodipine thus leading to an enhanced antitumor activity in leukemia".JOURNAL OF CONTROLLED RELEASE 112.2(2006):186-198.
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