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Objective To investigate the effect of muscone on malignant progression of ovarian cancer cells mediated by regulating sonic hedgehog (SHH) mediated autophagy. Methods Survival rates of human ovarian cancer cell line SKOV3 treated with 0, 2, 4, 8, 16, and 24 µmol/L muscone were detected, and the optimal cell action concentration of muscone was selected. SKOV3 cells were cultured in vitro, and their transplanted tumor mouse models were constructed. Cells were randomly grouped into the control group, the muskone group, the muskone+chloroquine (CQ，an autophagy inhibitor) group, the muskone+empty group and the muskone+SHH overexpression group. After grouping and treatment with musconeand, CQ, empty plasmid and SHH overexpression plasmid, the tumor volume and weight in transplanted tumor mice were detected. EdU staining, TUNEL staining, cell scratch, Transwell invasion assay, immunoblotting and real-time fluorescence quantitative PCR were used to detect proliferation, apoptosis, migration and invasion of SKOV3 cells, the expression of autophagy related proteins (LC3Ⅱ/LC3Ⅰ, Beclin-1) and SHH in SKOV3 cells and transplanted tumor mice in each. Results Compared with the control group, the cell proliferation rate, cell migration rate, number of invasions, tumor volume and weight, and the expression of SHH mRNA and protein in tumor tissue were decreased in the muskone group (P＜ 0.05), and the apoptosis rate, LC3Ⅱ/LC3Ⅰ, Beclin-1 protein in cells and tumor tissue were increased (P＜0.05). Compared with the muscone group, the cell proliferation rate, cell migration rate, number of invasion, tumor volume and weight were increased in the muscone+CQ group and the muskone+SHH overexpression group (P＜0.05), and the apoptosis rate, LC3Ⅱ/ LC3Ⅰ and the expression of Beclin-1 protein in cells and tumor tissue were decreased (P＜0.05). There were no significant differences in the above indicators in the muscone+empty group (P＞0.05). Conclusion Muscone can promote autophagy of ovarian cancer cells by down-regulating SHH, thereby inhibiting their proliferation, in vivo growth, migration and invasion, promoting their apoptosis, and ultimately inhibiting their malignant progression. [ABSTRACT FROM AUTHOR]

Objective To investigate effects of malt extract (ME) on the proliferation and secretion of prolactin (PRL) in anterior pituitary cells of hyperprolactinemia (HPRL) rats by regulating the Nod-like receptor protein 3(NLRP3)/ cysteine aspartic specific protease-1 (Caspase-1)/ interleukin-1β (IL-1β) pathway. Methods The anterior pituitary cells of normal and HPRL rats were separated and named as the NC group and the model group. The expression levels of growth hormone and PRL in cells were identified by immunohistochemistry. Cells in the model group were treated with 0 mg/L ME, 25 mg/L ME, 50 mg/L ME, 100 mg/L ME, 5 mmol/L Adenosine 5'-triphosphate (ATP), 100 mg/L ME and 5 mmol/L ATP for 48 h, and named as the Blank group, the ME low dose group (ME-L group), the ME medium dose group (ME-M group), the ME high dose group (ME-H group), the ATP (NLRP3 activator) group and ME-H+ATP group. The morphology of cells in each group was observed by light microscope. Cell proliferation was detected by CCK-8 method. Cell apoptosis was detected by flow cytometry. The level of PRL in the supernatant of rat anterior pituitary cells was detected by ELISA. Western blot assay was applied to detect expression levels of proliferating cell nuclear antigen (PCNA), dopamine receptor D2 (DRD2), dopamine transporter (DAT), NLRP3, Caspase-1 and IL-1β in rat anterior pituitary cells. Results Rat anterior pituitary cells were isolated successfully. Compared with the NC group, the volume of anterior pituitary cells was smaller and the shape was irregular, the OD450 value, prolactin level, DAT, PCNA, NLRP3, Caspase-1, IL-1β protein expression increased, and the apoptosis rate and DRD2 protein expression decreased in the blank group (P＜0.05). Compared with the blank group, the morphology of anterior pituitary cells was improved in the ME-L group, the ME-M group and the ME-H group. The OD450 value, prolactin level, DAT, PCNA, NLRP3, Caspase-1 and IL-1β protein expression levels decreased, and the apoptosis rate and DRD2 protein expression increased in a dose-dependent manner. The change trend of the corresponding indexes was contrary to the above in the ATP group (P＜0.05). ATP attenuated the inhibitory effect of high-dose ME on the proliferation of anterior pituitary cells and PRL secretion in HPRL rats. Conclusion ME may inhibit the proliferation and PRL secretion of HPRL rat anterior pituitary cells by down-regulating the NLRP3/Caspase-1/IL-1β pathway. [ABSTRACT FROM AUTHOR]