Effect of Scutellarin on Promoting the Sensitivity of Breast Cancer 4T1 Cells to Cisplatin in Vitro and in Vivo

To detect the effect of scutellarin (SCU) on promoting the sensitivity of breast cancer 4T1 cells to cisplatin (CDDP), and the molecular mechanism as well. CCK-8, scratch assay, Transwell assay and flow cytometry were employed to investigate the effects of SCU combined with CDDP on the proliferation, migration, invasion and apoptosis of 4T1 cells in vitro. Then, the 4T1 tumor-bearing mouse model was established to explore the effect of SCU combined with CDDP on tumor growth in vivo. The morphology, necrotic area and microvascular density of tumor tissues were observed by H&E staining. Real-time fluorescence quantitative PCR and Western Blot were used to detect the mRNA and proteins expression of apoptosis factors in tumor tissues. The results showed that SCU (200 μmol/L) combined with CDDP (80 μmol/L) significantly inhibited the in vitro proliferation of 4T1 cells (P<0.01). Moreover, the migration and invasion capacity of 4T1 cell were apparently reduced and the apoptosis of tumor cells were significantly promoted when treated with SCU (200 μmol/L) combined with CDDP (80 μmol/L) (P<0.01). Besides, the growth of 4T1 cells in vivo was remarkably slower after administration of 60 mg/kg SCU combined with 3.0 mg/kg CDDP (P<0.01). Further H&E semi-quantitative results revealed the microvascular density of 4T1 tumor tissues was significantly decreased (P<0.01). What’s more, the combination of SCU and CDDP significantly promoted the expression of pro-apoptotic factors Caspase-3, Bax, Caspase-9, Cleaved-Caspase-3 and Cleaved-Caspase-9 (P<0.01) and inhibited the expression of anti-apoptotic factor Bcl-2 in tumor tissues (P<0.05). In conclusion, SCU combined with CDDP could inhibit the function of tumor cells by enhancing the sensitivity of 4T1 cells to CDDP, and also regulate the expression of apoptosis factors, thus inhibiting the growth of tumor.