Hung Huey-Shan, Wu Wen-Jun, Cheng Ya-Wen, Wu Tsu-Chin, Chang Kee-Lung, Lee Huei
Institute of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan, ROC.
Mutat Res. 2007 Apr 2;628(2):107-16. doi: 10.1016/j.mrgentox.2006.12.005. Epub 2006 Dec 22.
Cooking oil fumes (COF) have been shown to be associated with lung cancer incidence in Chinese women. Our recent report indicates that inhibitor of apoptosis protein 2 (IAP2) induced by COF may contribute to the survival and proliferation of A549 lung cancer cells. In this study, to further verify whether other antiapoptosis proteins including IAP1, X-linked IAP (XIAP), and survivin, were linked with lung cancer cell survival and proliferation, these IAPs expressions in A549 cells after treatment with COF and its two major components, benzo[a]pyrene (BaP) and 2,4-decadienal (2,4-DDE) were evaluated by Western blotting. Our data showed that IAP2 was significantly induced by COF, BaP, and 2,4-DDE, but XIAP was decreased by COF and 2,4-DDE, but not by BaP. Even though different effects of COF and 2,4-DDE on IAP2 and XIAP protein expressions were observed, the caspase-3 expression was diminished by COF and 2,4-DDE. In addition, induction of IAP2 and phosphorylated Akt proteins by COF and 2,4-DDE were simultaneously abolished by LY294002. Flow cytometry and terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) analysis showed that the proportion of A549 cells at the S-phase was increased significantly after treatment with COF or 2,4-DDE. The cell proliferation induced by COF is associated with the attenuation of p21(Cip/Waf1) expression. Therefore, increases of IAP1, IAP2, survivin, and cyclin D1 expressions and decreases of XIAP, caspase-3, and p21 expressions might partly contribute to the survival and proliferation of lung cancer cells after exposure to 2,4-DDE and COF. In conclusion, the lung cancer cell growth promoted by COF might support previous epidemiological reports indicating that exposure of COF was associated with lung cancer development among Chinese women.
食用油油烟（COF）已被证明与中国女性肺癌发病率有关。我们最近的报告表明，COF诱导的凋亡抑制蛋白2（IAP2）可能有助于A549肺癌细胞的存活和增殖。在本研究中，为了进一步验证包括IAP1、X连锁凋亡抑制蛋白（XIAP）和生存素在内的其他抗凋亡蛋白是否与肺癌细胞的存活和增殖有关，通过蛋白质免疫印迹法评估了COF及其两种主要成分苯并[a]芘（BaP）和2,4-癸二烯醛（2,4-DDE）处理后A549细胞中这些IAP的表达。我们的数据表明，COF、BaP和2,4-DDE显著诱导IAP2，但COF和2,4-DDE使XIAP降低，而BaP则不然。尽管观察到COF和2,4-DDE对IAP2和XIAP蛋白表达有不同影响，但COF和2,4-DDE均使半胱天冬酶-3表达减少。此外，LY294002同时消除了COF和2,4-DDE对IAP2和磷酸化Akt蛋白的诱导作用。流式细胞术和末端脱氧核苷酸转移酶介导的dUTP缺口末端标记（TUNEL）分析表明，用COF或2,4-DDE处理后，A549细胞处于S期的比例显著增加。COF诱导的细胞增殖与p21（Cip/Waf1）表达的减弱有关。因此，IAP1、IAP2、生存素和细胞周期蛋白D1表达的增加以及XIAP、半胱天冬酶-3和p21表达的降低可能部分促成了肺癌细胞在暴露于2,4-DDE和COF后的存活和增殖。总之，COF促进的肺癌细胞生长可能支持先前的流行病学报告，即COF暴露与中国女性肺癌发生有关。
