Walterinnesia aegyptia venom combined with silica nanoparticles enhances the functioning of normal lymphocytes through PI3K/AKT, NFκB and ERK signaling.
Walterinnesia aegyptia venom combined with silica nanoparticles enhances the functioning of normal lymphocytes through PI3K/AKT, NFκB and ERK signaling.
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DOI：
10.1186/1476-511x-11-27
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发表时间：
2012-02-15
影响因子：
4.5
通讯作者：
Daghestani M
中科院分区：
文献类型：
--
作者：
Badr G;Al-Sadoon MK;El-Toni AM;Daghestani M
蛇毒的毒性在某些物种中随时间而变化。新生蛇和幼蛇的毒液似乎比同一物种的成年蛇更强，而且最近没有进食的蛇的咬伤，比如刚刚从冬眠中出来的蛇，比最近进食的蛇更危险，因为注射的毒液量更大。因此，蛇毒的效力通常是用LD50或IC50测试来确定的。本研究研究了埃及Walterinnesia aegyptia （WEV）蛇毒对人乳腺癌细胞株MDA-MB-231的抗肿瘤作用，以及对正常小鼠外周血单个核细胞（PBMCs）的影响。这种毒液被单独使用（WEV）或与二氧化硅纳米颗粒（WEV+NP）结合使用。测定WEV单独作用和WEV+NP作用于MDA-MB-231细胞的IC50值分别为50 ng/ml和20 ng/ml。有趣的是，在这些浓度下，毒液并没有影响正常人类pbmc的生存能力。为了进一步研究该毒液在体内的作用，我们采用三组小鼠（每组15只）：第一组为对照组，第二组皮下注射WEV，第三组注射WEV+NP。通过流式细胞术和western blot分析，我们发现wev注射小鼠的血液淋巴细胞通过激活AKT、NF-κB和ERK来响应CXCL12，肌动蛋白聚合和细胞骨架重排明显增加。与对照组相比，这些淋巴细胞在有丝分裂原刺激下的增殖能力显著增加（P < 0.05）。更重要的是，与WEV处理小鼠相比，WEV+ np处理小鼠正常淋巴细胞的生物学功能显著增强（P < 0.05）。我们的数据揭示了WEV独特的生物效应，我们证明了它与纳米颗粒的结合可以增强这些生物效应。
The toxicity of snake venom varies over time in some species. The venom of newborn and small juvenile snakes appears to be more potent than adults of the same species, and a bite from a snake that has not fed recently, such as one that has just emerged from hibernation, is more dangerous than one that has recently fed due to the larger volume of venom injected. Therefore, the potency of a snake's venom is typically determined using the LD50 or IC50 tests. In the present study, we evaluated the anti-tumor potential of snake venom from Walterinnesia aegyptia (WEV) on the human breast carcinoma cell line MDA-MB-231, as well as its effect on the normal mice peripheral blood mononuclear cells (PBMCs). This venom was used alone (WEV) or in combination with silica nanoparticles (WEV+NP). The IC50 values of WEV alone and WEV+NP in the MDA-MB-231 cells were determined to be 50 ng/ml and 20 ng/ml, respectively. Interestingly, at these concentrations, the venom did not affect the viability of normal human PBMCs. To investigate the in vivo effects of this venom further, three groups of mice were used (15 mice in each group): Group I was the control, Group II was subcutaneously injected with WEV, and Group III was injected with WEV+NP. Using flow cytometry and western blot analysis, we found that the blood lymphocytes of WEV-injected mice exhibited a significant increase in actin polymerization and cytoskeletal rearrangement in response to CXCL12 through the activation of AKT, NF-κB and ERK. These lymphocytes also showed a significant increase in their proliferative capacity in response to mitogen stimulation compared with those isolated from the control mice (P < 0.05). More importantly, in the WEV+NP-treated mice, the biological functions of normal lymphocytes were significantly (P < 0.05) enhanced in comparison with those of WEV-treated mice. Our data reveal the unique biological effects of WEV, and we demonstrated that its combination with nanoparticles strongly enhanced these biological effects.