ABSTRACT
Purpose@#Effective predictors of the response to neoadjuvant chemotherapy (NAC) are still insufficient. This study aimed to investigate the predictive value of serum lipid profiles for the response to NAC in breast cancer patients. @*Methods@#A total of 533 breast cancer patients who had received NAC were retrospectively studied. The pretreatment of serum lipids, including total cholesterol (TC), triglycerides (TG), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), and lipoprotein-α, and clinicopathological characteristics were collected to assess their predictive roles. @*Results@#Breast cancer patients had significantly lower TC, TG, HDL-C, and LDL-C levels than normal individuals. Among these indicators, TG and LDL-C levels and HDL-C level increased and decreased significantly after NAC, respectively. In estrogen receptor (ER)-positive patients, increased LDL-C level was associated with better outcomes. Moreover, the receiver operating characteristic curve analyses suggested that TG and HDL-C levels at diagnosis can be used as predictors of the response to NAC only in the ER-positive subgroup.According to univariate analyses, patients with low TG level (< 1.155 mmol/L) or high HDL-C level (≥ 1.305 mmol/L) in the ER-positive subgroup had more favorable clinical responses than the other patients in the subgroup. Furthermore, according to multivariate analyses, a high HDL-C level (≥ 1.305 mmol/L, p = 0.007) was an independent predictor of NAC efficacy. @*Conclusion@#High HDL-C level (≥ 1.305 mmol/L) before NAC and increased LDL-C level after NAC were associated with the better treatment response in ER-positive breast cancer patients.These results are potentially considered beneficial in establishing treatment decisions.
ABSTRACT
Objective: To observe the activation effect of sulfasalazine on ferroptosis of breast cancer ZR-75-1 cells, and to explore its possible mechanism. Methods: The different concentrations of sulfasalazine (0, 1.0, 0.5, 1.0, and 2.0 mmol/L) were used to treat ZR-75-1 cells. The morphological change of ZR-75-1 cells was observed under an inverted microscope. The proliferation inhibitory rate of ZR-75-1 cells was detected by CCK-8 method. The expression levels of glutathione peroxidase 4 (GPX4) and cysteine-glutamate antiporter subunit (xCT) proteins in ZR-75-1 cells were detected by Western blotting. The fluorescent probe was used to label the ZR-75-1 cells treated with different concentrations of sulfasalazine, then the change of reactive oxygen specie (ROS) level (as indicated by fluorescence intensity) was detected by FCM method. The expression level of divalent metal transporter 1 (DMT1) mRNA was detected by real-time fluorescent quantitative PCR. Results: Sulfasalazine caused the morphological changes and death of ZR-75-1 cells. The low doses of sulfasalazine had little effect on the proliferation of ZR-75-1 cells (P > 0.05), but the high concentrations of sulfasalazine inhibited cell proliferation significantly (P < 0.05). The high concentrations of sulfasalazine inhibited the expressions of GPX4 and xCT proteins in ZR-75-1 cells (both P < 0.05), and also promoted the accumulation of intracellular ROS (P < 0.05). Sulfasalazine increased the expression of DMT1 mRNA in ZR-75-1 cells (P < 0.05). Conclusion: Sulfasalazine can increase the accumulation of ROS by inhibiting the expressions of GPX4 and xCT proteins to induce the ferroptosis of ZR-75-1 cells. In which, the activation of DMT1 expression may be one of the mechanism.