山竹子素通过调控PTEN在宫颈癌中发挥抑癌作用  

Garcinol exerts the cancer-inhibiting role in cervical cancer through regulation of PTEN

作　　者：冯思芳[1] 赵娟[2] 杨婷[2] 李琛[2] 李龙[2] FENG Sifang;ZHAO Juan;YANG Ting;LI Chen;LI Long(Department of Respiratory and Critical Care Medicine;Department of Obstetrics and Gynecology,the First Affiliated Hospital of Xi'an Jiaotong University,Shaanxi Xi'an 710061,China)

机构地区：[1]西安交通大学第一附属医院呼吸与危重症医学科,陕西西安710061 [2]西安交通大学第一附属医院妇产科,陕西西安710061

出　　处：《现代肿瘤医学》2024年第2期234-240,共7页Journal of Modern Oncology

基　　金：西安交通大学第一附属医院科研发展基金(编号:2021ZXY-16)。

摘　　要：目的:探讨山竹子素是否通过调控PTEN在宫颈癌中发挥抑癌作用。方法:Immunoblotting检测PTEN表达水平。利用CRISPR/Cas9技术建立PTEN敲除的宫颈癌细胞模型。CCK-8和EdU染色方法检测细胞生长和增殖。流式细胞术检测细胞凋亡水平。划痕实验检测细胞迁移。Transwell实验检测细胞侵袭。利用PTEN敲除宫颈癌细胞来构建荷瘤小鼠模型,检测山竹子素对肿瘤形成和生长的影响。免疫组化检测移植瘤组织中PTEN表达和Ki-67增殖水平。结果:山竹子素可以显著上调宫颈癌细胞中PTEN的蛋白表达水平(P<0.01)。转染Cas9-PTEN质粒至宫颈癌细胞中可以显著下调PTEN表达(P<0.01)。在野生型宫颈癌细胞中,山竹子素可以显著抑制细胞的增殖、迁移和侵袭,同时诱导细胞凋亡(P<0.01)。在PTEN敲除的宫颈癌细胞中,山竹子素则对宫颈癌细胞增殖、迁移、侵袭和凋亡,无明显影响(P>0.05)。PTEN敲除可阻断山竹子素对裸鼠体内异种移植瘤生长的抑制作用。结论:山竹子素通过调控PTEN在宫颈癌中发挥抑癌作用。Objective:To investigate whether garcinol exerts the cancer-inhibiting role in cervical cancer through regulation of PTEN.Methods:PTEN expression was measured by immunoblotting.PTEN-knockout(KO)cervical cancer cells were established using CRISPR/Cas9 technology.Cell growth and proliferation were detected by CCK-8 assay and EdU assay.Cell apoptosis was assessed by flow cytometry.Cell migration was measured by wound-healing assay.Cell invasion was evaluated by Transwell assay.Xenograft tumors in nude mice derived from PTEN-KO cells were applied to assess the effect of garcinol on tumor growth.PTEN expression and Ki-67 proliferative index in xenograft tumors were determined by immunohistochemical staining.Results:Treatment with garcinol significantly upregulated the expression of PTEN protein in cervical cancer cells(P<0.01).PTEN was markedly knocked out in cells transfected with Cas9-PTEN vectors(P<0.01).In wild-type cervical cancer cells,garcinol was able to inhibit cell proliferation,migration and invasion,and induce cell apoptosis(P<0.01).In PTEN-KO cervical cancer cells,garcinol showed no obvious effect on cell proliferation,migration,invasion and apoptosis(P>0.05).PTEN-KO blocked the suppressive effect of garcinol on the growth of xenograft tumors in nude mice.Conclusion:Garcinol exerts the cancer-inhibiting role in cervical cancer through regulation of PTEN.

关 键 词：宫颈癌 山竹子素 PTEN CRISPR/Cas9 

分 类 号：R737.33[医药卫生—肿瘤]