新型溴苯取代的三氟甲基苯并环戊酮WW02对肺癌细胞增殖的影响及其分子机制

目的:探讨新型溴苯取代的三氟甲基苯并环戊酮WW02抑制人肺癌A549和H1299细胞活力及增殖的分子机制。方法:采用CCK-8和EdU法测定不同浓度的WW02(6.25、12.5、25、50μg/mL)对A549和H1299的细胞活力及增殖影响;不同浓度的WW02刺激A549和H1299细胞24h后,通过免疫印记(Westernblot)实验检测不同浓度WW02作用下Akt及mTOR磷酸化水平的变化;通过MOE Dock对WW02与Akt跟mTOR进行了分子对接。结果:用不同浓度(6.25、12.5、25、50μg/mL)WW02处理A549和H1299细胞后,A549及H1299细胞的活力较DMSO对照组呈浓度依赖性下降(P<0.05);细胞的增殖较DMSO对照组呈浓度依赖性下降(P<0.05)。与DMSO对照组相比,WW02刺激24h后,A549细胞中Akt及mTOR的磷酸化水平下降(12.5、12.5、25、50μg/mL WW02作用下,P<0.05);而与DMSO对照组相比,WW02刺激24h后H1299细胞中Akt及mTOR的磷酸化水平下降(25、50μg/mL WW02作用下,P<0.05);结合模式分析发现,WW02与Akt和mTOR结合较强,WW02与mTOR的最高打分为-8.3kcal/mol,而WW02与Akt的最高打分为-7.3kcal/mol。结论:WW02抑制肺癌A549及H1299细胞的活力与增殖,其作用机制可能通过直接结合Akt及mTOR蛋白进而抑制Akt及mTOR磷酸化来实现。

Stress corrosion cracking and its anisotropy of a PZT ferroelectric ceramics

Stress corrosion cracking (SCC) of a PZT ferroelectric ceramics in various media, such as moist at-mosphere, silicon oil, methanol, water and formamide, and its anisotropy have been investigated at constant load test using a single-edge notched tensile specimen. The results showed that SCC could occur in all media, and the threshold stress intensity factor of SCC in water and formamide, KISCC, revealed anisotropy. The KISCC for poling direction parallel to the crack plane, aISCC,Kwas greater than that perpendicular to the crack plane, bISCC,K similar to the anisotropy of fracture toughness KIC; however, the anisotropy factor of KISCC, which was abISCCISCC/KK=1.8 (in formamide) and 2.1 (in water), was larger than that of KIC, which is abICIC/KK=1.4. The stress-induced 90?domain switching causes the anisotropy of KIC and KISCC, besides, the resistance of SCC also has anisotropy.