Background
Perifosine is an inhibitor of Akt [1].
Perifosine is a synthetic antitumor alkylphospholipid. It induces cell apoptosis through inhibiting the activity of Akt. Perifosine shows antitumor activity in various cell lines including NSCLC, MM, epithelial carcinoma, prostate carcinoma and leukemia cells. In H460 cells, perifosine decreased cell survival and induced apoptosis with IC50 values of 1μM and 10 μM, respectively. The treatment of perifosine was also found to induce cleavage of caspase-8, caspase-9, caspase-3 and PARP in this cell line. In MM.1S cells, perifosine induced sub-G1 phase population increase from 15% to 57% at 10 μM and induced cleavage of caspase-8, caspase-9 and PARP in a dose-dependent manner. In mice inoculated with MM.1S cells, oral administration of perifosine significantly reduced MM tumor growth and increased survival [1, 2].
参考文献:
[1] Elrod H A, Lin Y D, Yue P, et al. The alkylphospholipid perifosine induces apoptosis of human lung cancer cells requiring inhibition of Akt and activation of the extrinsic apoptotic pathway. Molecular cancer therapeutics, 2007, 6(7): 2029-2038.
[2] Hideshima T, Catley L, Yasui H, et al. Perifosine, an oral bioactive novel alkylphospholipid, inhibits Akt and induces in vitro and in vivo cytotoxicity in human multiple myeloma cells. Blood, 2006, 107(10): 4053-4062.
Perifosine 是 Akt 的抑制剂 [1]。
Perifosine 是一种合成的抗肿瘤烷基磷脂。它通过抑制 Akt 的活性来诱导细胞凋亡。 Perifosine 在多种细胞系中表现出抗肿瘤活性，包括 NSCLC、MM、上皮癌、前列腺癌和白血病细胞。在 H460 细胞中，perifosine 降低细胞存活率并诱导细胞凋亡，IC50 值分别为 1μM 和 10 μM。还发现哌立福新处理可诱导该细胞系中 caspase-8、caspase-9、caspase-3 和 PARP 的裂解。在 MM.1S 细胞中，perifosine 在 10 μM 时诱导亚 G1 期细胞群从 15% 增加到 57%，并以剂量依赖的方式诱导 caspase-8、caspase-9 和 PARP 的裂解。在接种 MM.1S 细胞的小鼠中，口服哌立福新可显着降低 MM 肿瘤的生长并提高存活率 [1, 2]。
Protocol
| Cell experiment: [1] |
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Cell lines
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CRW22RV1 cells
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Preparation method
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The solubility of this compound in DMSO is
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Reaction Conditions
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10 μM, 24 hours
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Applications
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To assess the effect of perifosine on radiation-induced apoptosis, the Annexin-FITC based flow cytometry analysis was used. Both nuclear fragmentations with PI staining and translocated membrane phosphatidylserine (PS) with Annexin V staining were measured. Both perifosine and radiation induced significant apoptotic responses as shown by the increase of apoptotic cells. When radiation (6Gy) and perifosine (10 μM) were combined, the number of apoptotic cells was significantly increased. Perifosine alone did not induce cell cycle arrest at the G2/M phases and perifosine did not affect the IR-induced G2/M checkpoint.
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| Animal experiment: [1] |
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Animal models
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Male Athymic Nude-Foxn1nu mice injected with CRW22RV1 cells
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Dosage form
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Oral administration, in a loading dose of 300 mg/kg (2 × 150 mg/kg separated by 12 hours) followed by daily maintenance doses of 35 mg/kg for 5 days
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Applications
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Mice were separated into 4 groups: control, perifosine, radiotherapy and combined therapy. Perifosine alone did not have a significant effect on tumor growth. However, perifosine can significantly increase radiation induced tumor growth delay. To reach the 10-fold size of tumor volume to the initial volume in the control, it took 15, 19, 41 and 59 days in control, perifosine only, radiation only and combined treatment groups, respectively. It is noted that the combined treatment led to a complete remission of the CWR22RV1 tumor.
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Other notes
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Please test the solubility of all compounds indoor, and the actual solubility may slightly differ with the theoretical value. This is caused by an experimental system error and it is normal.
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参考文献:
[1] Gao Y, Ishiyama H, Sun M, et al. The alkylphospholipid, perifosine, radiosensitizes prostate cancer cells both in vitro and in vivo. Radiation oncology (London, England), 2011, 6: 39.
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