增塑剂DEHP通过JAK介导的Akt通路激活促进宫颈癌细胞的恶性生物学行为  

DEHP promotes the malignant biological behavior of cervical cancer cells through the JAK⁃mediated activation of the Akt pathway

作　　者：陈果 苏容玉 尹梓豪 龙胜文 魏晨曦 CHEN Guo;SU Rong-yu;YIN Zi-hao;LONG Sheng-wen;WEI Chen-xi(Laboratory of gene function and regulation,School of Life Sciences,Hunan Normal University,Changsha,Hunan 410081,China)

机构地区：[1]湖南师范大学生命科学学院,基因功能与调控研究实验室,湖南长沙410081

出　　处：《毒理学杂志》2024年第1期20-29,共10页Journal of Toxicology

基　　金：国家自然科学基金(21806036,81972642)。

摘　　要：目的 研究邻苯二甲酸二(2-乙基)己酯(DEHP)与宫颈癌细胞的恶性生物学行为之间的关系。方法 浓度梯度DEHP处理人子宫颈腺癌细胞Hela和鳞癌细胞Siha, CCK-8和克隆形成实验检测细胞活力,Hoechst 33258染色检测凋亡,划痕和transwell实验检测迁移和侵袭能力,通过Western blot检测相关蛋白的表达情况和磷酸化水平。同时使用荧光定量PCR技术检测Akt上游激酶JAK2的mRNA表达水平变化。最后通过DEHP与JAK 2抑制剂AG 490共处理,观察细胞的恢复情况。结果 经10~2和10~3 nmol/L DEHP暴露后,细胞的活力、迁移和侵袭能力明显提高,凋亡被抑制;细胞内Akt蛋白的磷酸化水平升高,上游JAK2表达上调。而JAK2抑制剂处理能缓解DEHP诱导的恶性生物学行为和Akt的磷酸化。结论 DEHP通过诱导JAK2的表达提高Akt蛋白的磷酸化水平,促进宫颈癌细胞的恶性生物学行为。Objective To study the relationship between di⁃2⁃ethylexgl phthalate(DEHP)and the malignant biological behavior of cervical cancer cells.Methods The common pathological types of cervical malignant tumors human cervical adenocarcinoma cells Hela and squamous carcinoma cells Siha were exposed to different concentrations of DEHP.CCK⁃8 and clone formation assay were performed for cell viability.Hoechst 33258 staining were used to indicate apoptosis.Scratches and transwell experiments were used to show migration and invasion ability.Meanwhile,the expression and phosphorylation levels of the relevant proteins were detected by Western blot.The mRNA expression level of the JAK2(Janus 2 kinase)was explored by RT⁃quantitative PCR.Finally,the recovery of cells was observed by co⁃treatment of DEHP with the JAK2 inhibitor AG 490.Results After exposure to 102nmol/L or 103 nmol/L DEHP,cell viability,migration and invasion were significantly increased,and apoptosis was inhibited.The phosphorylation level of Akt was increased and the upstream JAK2 was upregulated.However,the JAK2 inhibitor alleviated DEHP⁃induced malignant biological behavior and the phosphorylation of Akt.Conclusion DEHP enhances the phosphorylation of Akt protein by inducing the expression of JAK2 and promotes the malignant biological behavior of cervical cancer cells.

关 键 词：DEHP 宫颈癌 恶性生物学行为 JAK AKT 

分 类 号：R99[医药卫生—毒理学] R734.2[医药卫生—药学] R114