Baoshan branch, Renji Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai, China.
School of Life Science, Nantong University, Nantong, China.
Neoplasma. 2020 Jul;67(4):834-842. doi: 10.4149/neo_2020_190805N716. Epub 2020 May 6.
Breast cancer, especially triple-negative breast cancer, is one of the deadliest cancers in women. To date, there is a lack of a good therapeutic regimen for it. PPARγ has been reported to be a tumor suppressor and could be activated by many agonists involved in cancer inhibition. Therefore, the expression of PPARγ in breast cancer was analyzed by online software UALCAN whose data were from the TCGA database. The results revealed that the PPARγ expression was reduced in breast cancer tissues. Furthermore, the methylation in the PPARγ promoter was also assayed and the results indicated that the methylation level in the PPARγ promoter in breast cancer tissue was higher than that in normal tissue. In order to verify the methylation in promoter involved in the regulation of gene PPARγ expression, the 5'-Aza and fluorescence assays were performed and the results proved that methylation in promoter participated in gene PPARγ expression regulation. Pioglitazone, a PPARγ agonist, still was not investigated in breast cancer. Therefore, the effects of pioglitazone on breast cancer cells were tested by cell viability, scratch and transwell assays, and results indicated that the pioglitazone has the inhibition effect on the proliferation and migration of breast cancer cells by PPARγ which was correlated with the JAK2/STAT3 pathway. In order to further confirm the inhibition effect of pioglitazone on breast cancer in vivo, the nude mice model was administrated by gavage with pioglitazone. And the results indicated that pioglitazone could inhibit the growth of breast cancer in the PPARγ overexpression group in vivo. In summary, the expression of gene PPARγ was decreased in breast cancer tissues, which was correlated with its methylation in the promoter region. Moreover, pioglitazone could exert its inhibition on breast cancer proliferation and migration by the JAK2/STAT3 pathway.
乳腺癌，尤其是三阴性乳腺癌，是女性中最致命的癌症之一。迄今为止，针对这种疾病，还没有很好的治疗方案。据报道，PPARγ 是一种肿瘤抑制因子，可以被许多参与癌症抑制的激动剂激活。因此，通过在线软件 UALCAN 分析了乳腺癌中 PPARγ 的表达，其数据来自 TCGA 数据库。结果表明，乳腺癌组织中 PPARγ 的表达减少。此外，还检测了 PPARγ 启动子的甲基化，结果表明乳腺癌组织中 PPARγ 启动子的甲基化水平高于正常组织。为了验证启动子甲基化在调节基因 PPARγ 表达中的作用，进行了 5'-Aza 和荧光测定，结果证明启动子甲基化参与了基因 PPARγ 表达调控。吡格列酮是一种 PPARγ 激动剂，在乳腺癌中尚未进行研究。因此，通过细胞活力、划痕和 Transwell 测定测试了吡格列酮对乳腺癌细胞的作用，结果表明吡格列酮通过 PPARγ 对乳腺癌细胞的增殖和迁移具有抑制作用，这与 JAK2/STAT3 通路有关。为了进一步证实吡格列酮在体内对乳腺癌的抑制作用，通过灌胃给予裸鼠吡格列酮。结果表明，吡格列酮可以抑制体内 PPARγ 过表达组乳腺癌的生长。总之，基因 PPARγ 在乳腺癌组织中的表达降低，与启动子区域的甲基化有关。此外，吡格列酮可以通过 JAK2/STAT3 通路发挥其对乳腺癌增殖和迁移的抑制作用。
