Ovarian cancer is the most lethal gynecological cancer in women. Shikonin (SHK), derived from Lithospermum eryothrorhizon, can reduce cancer activity; however, its clinical effect on type 2 ovarian cancer cells remains undetermined. Here, we studied the effects of SHK on type 2 ovarian cancer using the KURAMOCHI, OVSAHO, CP70, and ascites E04 cell lines. The proliferation curve and half-maximal inhibitory concentration of SHK for the cell lines were evaluated using the second-generation tetrazolium dye assay and the cell viability were determined by the annexin V/PI as well as TUNEL assay. The caspase dependent pathway was performed by western blotting assay with pan-caspase inhibitor Z-VAD-FMK and SHK induced miR-874-3p expression thus suppressed anti-apoptosis markers XIAP and Bcl-xL. The effect of SHK on type 2 ovarian cancer cell migration and invasion was evaluated using the wound healing and transwell assays. Quantitative RT-PCR and western blot was used to evaluate cancer stem cell (CSC)-related gene/protein (OCT4, SOX2, NANOG, ALDH1, and C-MYC) expressions, sphere formation assay was executed and a xenograft animal model for in vivo antitumor effects of SHK. Taken together, Shikonin suppressed type 2 ovarian cancer cell viability, migration, and invasion abilities; decreased CSC-related markers expression as well as the sphere colony numbers. It also reduced the tumorigenicity of KURAMOCHI ALDH+ cells and induced anti-tumor effect in a xenograft model. Thus, SHK could contribute a potential therapeutic strategy on type 2 ovarian cancer cells via multiple functions.
Keywords: Shikonin; apoptosis; cancer stem cell; metastasis; miR-874-3p; type 2 ovarian cancer.
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