CAJ | 학술논문

以典型天然雌激素雌二醇为代表，以人体乳腺癌细胞 MCF-7增殖为手段，检验了六氯苯与雌二醇共同作用时的内分泌干扰活性及其机理。结果发现六氯苯具有强烈的内分泌干扰活性，但与雌二醇混合后，呈现明显的拮抗效应，内分泌干扰活性被显著抑制。机理分析表明六氯苯、雌二醇、二者混合物都可以干扰雌激素受体和胞外信号调节激酶(ERK)信号通路、激活转录因子、诱导细胞增殖。路径分析表明，六氯苯与雌二醇的拮抗作用与雌激素受体通路无关，主要原因是雌二醇降低了六氯苯对 ERK 的活化程度、降低了 p-ERK蛋白的表达、从而干扰了丝裂原活化蛋白激酶信号转导。转录因子分析表明，雌二醇弱化六氯苯内分泌干扰活性的主要原因是降低了 c-Myc 蛋白表达。上述发现为六氯苯的控制提供了理论依据。
이전형천연자격소자이순위대표，이인체유선암세포 MCF-7증식위수단，검험료륙록분여자이순공동작용시적내분비간우활성급기궤리。결과발현륙록분구유강렬적내분비간우활성，단여자이순혼합후，정현명현적길항효응，내분비간우활성피현저억제。궤리분석표명륙록분、자이순、이자혼합물도가이간우자격소수체화포외신호조절격매(ERK)신호통로、격활전록인자、유도세포증식。로경분석표명，륙록분여자이순적길항작용여자격소수체통로무관，주요원인시자이순강저료륙록분대 ERK 적활화정도、강저료 p-ERK단백적표체、종이간우료사렬원활화단백격매신호전도。전록인자분석표명，자이순약화륙록분내분비간우활성적주요원인시강저료 c-Myc 단백표체。상술발현위륙록분적공제제공료이론의거。
Hexachlorobenzene's (HCB's)estrogenicity change and potential mechanisms when mixing with a typical natural estrogen,17-Estradiol (E2),were investigated.Human breast cancer cell MCF-7 in-crease examination was used.The results showed that HCB had very strong estrogenicity,but the mixture of HCB and E2 showed strong rivalry effect,i.e.,E2 and HCB greatly weakened each other on endocrine disrupting effect.Mechanism analyses showed that E2 and HCB could interfere with the endocrine system via the endocrine receptor channel and the MAPK signal channel.The rivalry effect between E2 and HCB was unrelated with the traditional endocrine receptor channel,but depended strongly on the non-traditional ERK channel.E2 decreased the HCB activation of ERK protein,and decreased the expression of p-ERK protein,thus interrupting the transcription of MAPK signal.The transcription factor analyses showed that E2 weakened the function of HCB mainly by decreasing the expression of c-Myc protein.