The inhibition of the breast cancer by PPARγ agonist pioglitazone through JAK2/STAT3 pathway

Year, pages: 2020, 834 - 842

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.

Jiao, X., Lin, S., Lian, S., Qiu, Y., Li, Z., Chen, Z., Lu, W., Zhang, Y., Deng, L., Jiang, Y., Hu, G. 2020. The inhibition of the breast cancer by PPARγ agonist pioglitazone through JAK2/STAT3 pathway. In NEOPLASMA, vol. 67, no.4, pp. 834-842. 0028-2685. DOI: https://doi.org/10.4149/neo_2020_190805N716

Jiao, X., Lin, S., Lian, S., Qiu, Y., Li, Z., Chen, Z., Lu, W., Zhang, Y., Deng, L., Jiang, Y., Hu, G. (2020). The inhibition of the breast cancer by PPARγ agonist pioglitazone through JAK2/STAT3 pathway. NEOPLASMA, 67(4), 834-842. 0028-2685. DOI: https://doi.org/10.4149/neo_2020_190805N716

Publisher: AEPress, Ltd.