Hydroxysafflor yellow A sensitizes ovarian cancer cells to chemotherapeutic agent by decreasing WSB1 expression

Introduction: Carthamus tinctorius L. (safflower) is a traditional Chinese medicine, the active ingredient of which is hydroxysafflor yellow A (HSYA).(2) HSYA has been shown to have the potential to inhibit tumor growth. However, the molecular mechanisms whereby HSYA exerts its antitumor functions remain largely unclear. In this study, we investigated the antitumor mechanisms of HSYA in ovarian cancer cell line Skov3. Methods: The cell proliferation assay was conducted using a Cell Proliferation Assay kit. The cell viability assay was performed using the CellTiter-Blue Cell Viability kit. Microarray was conducted to identify the global gene expression change of ovarian cancer cells caused by HSYA treatment. Small interfering RNA (SiRNA)(3) transfection was conducted to knock down WD repeat and SOCS box-containing protein 1 (WSB1)(4). WSB1 expression was detected by quantitative reverse transcription-quantitative polymerase chain reaction (qRT-PCR)(5) The protein expression of extracellular signal-related kinase (Erk)(6)1/2 and phosphorylation-Erk1/2 was detected by western blot. Results: HSYA inhibited Skov3 cell proliferation in a dose-dependent manner (P < 0.05). When cells were cultured with HSYA and doxorubicin, cell viability was further reduced (P < 0.05). HSYA could decrease the expression of WSB1. Through knocking down of WSB1, ovarian cancer cell proliferation was inhibited and further reduced by treating with doxorubicin (P < 0.05), the expression of Erk1/2 and Erk phosphorylation were downregulated. Conclusion: HSYA may inhibit ovarian cancer cell line Skov3 proliferation and sensitize Skov3 cells to chemotherapeutic agents through the reduction of WSB1 expression.