Ding Boxiao, Chi Sung Gil, Kim Se Heon, Kang Suki, Cho Jae Ho, Kim Dong Su, Cho Nam Hoon
Department of Pathology, Yonsei University College of Medicine, Seoul, Korea.
J Cell Sci. 2007 Jul 1;120(Pt 13):2284-94. doi: 10.1242/jcs.002345. Epub 2007 Jun 13.
In HPV-positive cervical carcinoma cells, p53 protein is functionally antagonized by the E6 oncoprotein. We investigated a possible role of p53 in antioxidant defense of HPV-positive cervical cancer cell lines. We found that SiHa cells containing integrated HPV 16 had higher expression of p53 and exhibited the greatest resistant to H2O2-induced oxidative damage, compared with HeLa, CaSki and ME180 cell lines. Downregulation of p53 resulted in the inhibition of p53-regulated antioxidant enzymes and elevated intracellular ROS in SiHa cells. By contrast, the ROS level was not affected in HeLa, CaSki and ME180 cell lines after inhibition of the p53 protein. Under mild or severe H2O2-induced stress, p53-deficient SiHa cells exhibited much higher ROS levels than control SiHa cells. Furthermore, we analyzed cell viability and apoptosis after H2O2 treatment and found that p53 deficiency sensitized SiHa cells to H2O2 damage. Inhibition of p53 resulted in excessive oxidation of DNA; control SiHa cells exhibited a more rapid removal of 8-oxo-7,8-dihydro-2'-deoxyguanosine from DNA compared with p53-deficient SiHa cells exposed to the same level of H2O2 challenge. These data collectively show that endogenous p53 in SiHa cells has an antioxidant function and involves in the reinforcement of the antioxidant defense.
在人乳头瘤病毒（HPV）阳性的宫颈癌细胞中，p53蛋白在功能上被E6癌蛋白拮抗。我们研究了p53在HPV阳性宫颈癌细胞系抗氧化防御中的可能作用。我们发现，与HeLa、CaSki和ME180细胞系相比，含有整合型HPV 16的SiHa细胞p53表达更高，并且对H2O2诱导的氧化损伤表现出最大的抗性。p53的下调导致SiHa细胞中p53调节的抗氧化酶受到抑制，细胞内活性氧（ROS）水平升高。相比之下，在抑制p53蛋白后，HeLa、CaSki和ME180细胞系中的ROS水平未受影响。在轻度或重度H2O2诱导的应激下，p53缺陷的SiHa细胞表现出比对照SiHa细胞更高的ROS水平。此外，我们分析了H2O2处理后的细胞活力和凋亡情况，发现p53缺陷使SiHa细胞对H2O2损伤敏感。p53的抑制导致DNA过度氧化；与暴露于相同水平H2O2刺激的p53缺陷SiHa细胞相比，对照SiHa细胞表现出更快地从DNA中去除8-氧代-7,8-二氢-2'-脱氧鸟苷。这些数据共同表明，SiHa细胞中的内源性p53具有抗氧化功能，并参与增强抗氧化防御。
