Chen Dazhi, Carter Timothy H, Auborn Karen J
North Shore-Long Island Jewish Research Institute, 350 Community Drive, Manhasset, NY 11030, USA.
Anticancer Res. 2004 Sep-Oct;24(5A):2649-56.
Many tumors show dependence on estrogen for growth and establishment of drug resistance. We examined the effects of estrogen on cervical cancer cells exposed to apoptotic agents including drugs used for treatment.
We tested the effect of estradiol on apoptosis in three cervical cancer cell lines. Apoptosis was measured by endonucleolytic degradation of DNA. Bcl-2 was measured by Western analysis.
Estradiol reduced the percentage of cells undergoing apoptosis after exposure to the DNA-damaging agents UVB, mitomycin-C and cisplatin. Protection against taxol-induced apoptosis was marginal. Protection was independent of HPV gene expression, and not specific to apoptosis induced by DNA damage, since estradiol significantly reduced the number of apoptotic cells produced after exposure to indole-3-carbinol (I3C), a non-genotoxic phytochemical effective in preventing HPV-induced tumors. Higher concentrations of I3C overcame the anti-apoptotic effect of estradiol. Treatment with I3C resulted in loss of the survival protein Bcl-2, and estradiol partially reversed this effect.
Estrogen protects cervical cancer cells treated with DNA-damaging agents; UVB, mitomycin-C and cisplatin, from apoptotic death. For I3C, which induces apoptosis and is anti-estrogenic, the amount of apoptosis versus survival and the level of Bcl-2 depend on the I3C/estradiol ratio.
许多肿瘤在生长和产生耐药性方面表现出对雌激素的依赖性。我们研究了雌激素对暴露于包括治疗用药在内的凋亡诱导剂的宫颈癌细胞的影响。
我们检测了雌二醇对三种宫颈癌细胞系凋亡的影响。通过DNA的核酸内切酶降解来测定凋亡。通过蛋白质免疫印迹分析来测定Bcl-2。
雌二醇降低了暴露于DNA损伤剂紫外线B（UVB）、丝裂霉素-C和顺铂后发生凋亡的细胞百分比。对紫杉醇诱导的凋亡的保护作用微弱。这种保护作用不依赖于人乳头瘤病毒（HPV）基因表达，且并非特异性针对DNA损伤诱导的凋亡，因为雌二醇显著减少了暴露于吲哚-3-甲醇（I3C）后产生的凋亡细胞数量，I3C是一种对预防HPV诱导的肿瘤有效的非基因毒性植物化学物质。更高浓度的I3C克服了雌二醇的抗凋亡作用。用I3C处理导致存活蛋白Bcl-2丧失，而雌二醇部分逆转了这种作用。
雌激素保护经DNA损伤剂UVB、丝裂霉素-C和顺铂处理的宫颈癌细胞免于凋亡死亡。对于诱导凋亡且具有抗雌激素作用的I3C，凋亡与存活的比例以及Bcl-2的水平取决于I3C/雌二醇的比例。
