Src Inhibition Can Synergize with Gemcitabine and Reverse Resistance in Triple Negative Breast Cancer Cells via the AKT/c-Jun Pathway

• DOI: 10.1371/journal.pone.0169230
• Publication Date: 2017-01-09T22:15:23Z
• Authors: Zhen-Hua Wu; Chen Lin; Ming-Ming Liu; Jian Zhang; Zhong-Hua Tao; Xi-Chun Hu
• Keywords: Triple-negative breast cancer

Purpose Gemcitabine-based chemotherapy remains one of the standards in management metastatic breast cancer. However, intrinsic and acquired resistance to gemcitabine inevitably occurs. The aims this study were assess efficacy combination src inhibition gemcitabine-resistant cancer cells. Methods Results By using colony formation, sphere forming, flow cytometry, cell counting kit-8 transwell assays, 231/GEM-res (gemcitabine-resistant) line, which was 10 times more resistant, shown have elevated drug tolerance, enhanced proliferative self-renewal abilities, compared with its parental Inhibition by both saracatinib (AZD0530) siRNA could partially reverse attenuate resistance-associated anti-apoptosis, migration stem capacities. In addition, had synergistic antitumor effects. Western blot analysis revealed up-regulation pro-apoptotic protein BAX, along down-regulation anti-apoptotic proteins (BCL-XL, Survivin), associated (p-FAK, MMP-3) (CSC) markers (CD44, Oct-4), probably mediated AKT/c-Jun pathway. Conclusion highly 231 cells, can synergize gemcitabine, resistance, inhibit tumor growth/metastasis/stemness possibly via