Methyl Protodioscin Downregulates SORT1 and Enhances Carboplatin Sensitivity in A2780 Ovarian Cancer Cells

Abstract

Background: Ovarian cancer is the most common lethal cancer of the female reproductive system and is often diagnosed in advanced stages. The Sortilin 1 (SORT1) gene is overexpressed in ovarian cancer cells. Methyl protodioscin, an herbal bioactive compound, has significant antitumor activities. Objectives: Considering the necessity of identifying new medicinal agents and treatments in ovarian cancer, this project investigated the effects of methyl protodioscin on the expression of the SORT1 gene and the response to chemotherapy in the ovarian cancer cell line (A2780 S). Methods: The viability of ovarian cancer cells (A2780) after treatment with methyl protodioscin (800, 400, 200, 100, 50, 25, 12.5, 6.25, and 3.12 µM) was evaluated by MTT assay, trypan blue staining, and lactate dehydrogenase activity measurement. The expression level of the SORT1 gene was investigated by real-time PCR. The effect of simultaneous treatment with methyl protodioscin and the chemotherapy drug carboplatin on cell viability was measured. Results: After 24, 48, 72, and 96 hours of treatment, methyl protodioscin significantly decreased cell viability in a concentration- and time-dependent manner (P < 0.05). After 24 hours, treatment with the IC50 concentration of methyl protodioscin (14.5 µM) caused a significant decrease in SORT1 expression in ovarian cancer cells by 33% (P < 0.05). The combination of methyl protodioscin with carboplatin decreased cell viability with a synergistic effect. Conclusions: Methyl protodioscin had an inhibitory effect on the survival of ovarian cancer cells in a concentration- and time-dependent manner and reduced the expression of the SORT1 gene. Additionally, this herbal compound synergistically increased the toxicity of carboplatin.