The effects of Stattic and/or Paclitaxel on triple negative breast cancer

Triple negative breast cancer (TNBC) is an invasive and metastatic cancer with aggressive progress. We aimed to investigate the in vitro and in vivo antiproliferative and in vivo antimetastatic effects of Paclitaxel, used alone or in combination with Stattic, a STAT-3 inhibitor, in experimental TNBC models. The effects of different concentrations of Stattic and/or Paclitaxel on cell viability on 4T1 TNBC cell line were determined by MTT test, and phospho- STAT1/STAT1 and phospho-STAT3/STAT3 levels were determined by ELISA method. In vivo experimental model was created by subcutaneous administration of 4T1 cells to the mammary tissue of female BALB/c mice. Saline, DMSO and Stattic were administered to the experimental groups every other day and Paclitaxel was administered intraperitoneally every three days. Body weights and tumor diameters were measured every three days. After sacrification, phospho-STAT1/STAT1, phospho-STAT3/STAT3, TAS, TOS, iNOS and VEGF levels in lung and tumor tissue were determined by ELISA and histopathological analysis was performed. The difference between groups was assessed at P<0.05 with Kruskal-Wallis test. Stattic application decreased cell viability in both cell lines dose-dependently (time independent) (P<0.05). Co-administration decreased the amount of viable cells with an additive effect depending on the dose and time. With the increase in the application time, the amount of viable cells was affected due to the changes in the STAT1 pathway, independent of the STAT3 pathway. There were no significant differences in body weights, tumor diameter, tumor weight and body temperature between groups in in vivo studies. While Paclitaxel and/or Stattic applications did not make a difference in STAT3, STAT1, iNOS, OSI and VEGF levels in tumor tissue, iNOS, OSI and VEGF levels increased in parallel with the increasing trend in STAT3 levels in lung tissue. Co-administration increased metastasis to the lung by affecting the STAT1 pathway.