Lysophosphatidic Acid Down-regulated SKOV3 Cells of Ovarian Cancer in Doxorubicin Hydrochloride-induced Apoptosis / 中国生物化学与分子生物学报

ABSTRACT

Lysophosphatidic acid (LPA), a bioactive lipid medium, plays an important role in the development and progression of ovarian cancer. Doxorubicin hydrochloride (DOX) is a first-line drug in the ovarian cancer clinical therapy, while the effect and molecular mechanism of LPA in the ovarian cancer with DOX treatment is still unclear. This study intended to explore the effect and molecular mechanism of LPA in ovarian cancer treated with DOX. SKOV3 and OVCAR-3 cells of human ovarian cancer and Chinese hamster ovary cells were treated with control, LPA (lOp-mol/L), DOX (2jjLmol/L) and LPA (10jJLmol/L) + DOX (2p,mol/L) respectively for 24 hours. The morphological changes of SKOV3 cells were observed under optical microscope and transmission electron microscope. Results showed that LPA reduced cell death and the degree of chromatin aggregation in SKOV3 cells treated with DOX; RT-qPCR showed that LPA treatment could down-regulate the mRNA levels of caspase-3 in DOX-treated SKOV3 cells (P<0. 05); Western blot showed that LPA treatment could reduce caspase-3 and cleaved caspase-3 levels treated with DOX in SKOV3, OVCAR-3 and CHO cells (P<0. 05); Flow cytometry using Annexin V/PI double staining showed that LPA could down-regulate apoptosis in SKOV3 cells treated with DOX (P<0. 05); DCFH-DA method was used to detect intracellular levels of reactive oxygen species (ROS) in SKOV3 cells. It was found that LPA reduced the intracellular ROS level treated with DOX (P<0. 05). Our preliminarily study showed the effect of LPA in the apoptosis of ovarian cancer treated with DOX, which may provide a reference for the drug therapy of ovarian cancer targeting LPA.