Fischer Juliana de Saldanha da Gama, Carvalho Paulo Costa, Gattass Cerli Rocha, Paschoal Eduardo Marcos Machado, da Mota e Silva Marcelo Soares, Carvalho Maria da Gloria da Costa
Molecular Oncology Laboratory University Hospital Clementino Fraga Filho, Federal University of Rio de Janeiro (HUCFF-UFRJ), Brazil.
J Exp Ther Oncol. 2006;5(4):301-7.
The K-Ras protein is found mutated in 42.4% of lung adenocarcinoma cases, evidencing its importance as a chemotherapeutic target. The Ras protein becomes functional after farnesylation, a post-transduction modification, allowing its attachment to the cellular membrane permitting signal transduction. Perillyl alcohol (POH) has been shown to inhibit the farnesylation of small G-proteins such as Ras. HSP70, a protein known to appear after heat shock (HS), is found over expressed in lung cancer and modifies chemotherapeutic effects. In this work, the effect of POH and HS in the gene expression of human adenocarcinoma lung cells (A549) is studied. Cells incubated with POH followed by 42 degrees C HS presented a 20.7% cellular viability decrease compared to the ones kept at 37 degrees C. A different pattern synthesis was observed for each sequences of cell treatment. Independent of the heat treatment, the amount of HSP70 was decrease by POH without modification in the amount of p53. Here it is shown that HS modified the POH effects in the ERK activation pathway by altering the phosphorylation of p44/42 in human adenocarcinoma lung cells.
在42.4%的肺腺癌病例中发现K-Ras蛋白发生突变,这证明了其作为化疗靶点的重要性。Ras蛋白在法尼基化(一种转导后修饰)后变得有功能,使其能够附着在细胞膜上从而进行信号转导。紫苏醇(POH)已被证明可抑制诸如Ras等小G蛋白的法尼基化。HSP70是一种在热休克(HS)后出现的蛋白,在肺癌中过度表达并改变化疗效果。在这项工作中,研究了POH和HS对人肺腺癌细胞(A549)基因表达的影响。与在37℃培养的细胞相比,先用POH处理然后在42℃进行热休克处理的细胞存活率降低了20.7%。对于每种细胞处理顺序都观察到了不同的模式合成。与热处理无关,POH可降低HSP70的量,而p53的量没有改变。在此表明,热休克通过改变人肺腺癌细胞中p44/42的磷酸化来改变POH在ERK激活途径中的作用。