Abstract
BackgroundMelanoma is among the most aggressive types of skin malignancy and can have an unpredictable clinical course. Exploration of novel therapeutic targets and their regulators remains essential for the prevention and treatment of melanoma.MethodsHSDL2 protein levels were examined by immunohistochemistry. The roles of HSDL2 in cell proliferation and apoptosis were identified by CCK-8 and colony formation assays. The function of HSDL2 in cell apoptosis was analysed by flow cytometry. Western blotting, cell proliferation and apoptosis and a xenograft tumour model were utilized to explore the inhibitory functions and mechanisms of CuE in melanoma.ResultsHSDL2 is overexpressed in melanoma and promotes melanoma progression by activating the ERK and AKT pathways. CuE could inhibit the ERK and AKT pathways by decreasing HSDL2 expression; therefore, CuE could inhibit melanoma growth in vitro and in vivo.ConclusionHSDL2 may be a promising therapeutic target against melanoma, and CuE can inhibit melanoma by downregulating HSDL2 expression.
Highlights
Skin cancer is the most common type of cancer in dermatology [1], and melanoma is one of the most fatal forms and is the fifth most common cancer in men and the sixth in women [2, 3]
We found that Hydroxysteroid dehydrogenase-like 2 (HSDL2) promoted cell proliferation and suppressed apoptotic cell death by activating the AKT and Extracellular signal-regulated kinase (ERK) signalling pathways and that Cucurbitacin E (CuE) could slow melanoma growth by inhibiting the AKT and ERK signalling pathways via the downregulation of HSDL2 expression
HSDL2 knockdown inhibited the AKT and ERK signaling pathways in melanoma cells To investigate the mechanisms by which HSDL2 regulated melanoma growth, we examined the activation of multiple signal transduction pathways involved in cell growth and survival in A375 cells after HSDL2 knockdown using the PathScan Stress and Apoptosis Signaling Antibody Array Kit and RTK Signaling Antibody Array Kit
Summary
Skin cancer is the most common type of cancer in dermatology [1], and melanoma is one of the most fatal forms and is the fifth most common cancer in men and the sixth in women [2, 3]. Previous studies have shown that HSDL2 is involved in lipid metabolism and the synthesis of cholesterol [8, 9], displaying significant protumour function by promoting cell proliferation and inhibiting apoptosis [10, 11], and has been reported to be associated with some cancers, such as pancreatic. To date, the function of HSDL2 in melanoma remains unclear. Natural compounds found in vegetables, fruits, and medicinal plants have been considered potential sources of inhibitors for cancer [15]. The potential anticarcinogenic properties of CuE on diverse tumour types, such as gastric cancer, lung cancer, breast cancer and ovarian cancer, have been well studied [18,19,20,21]. The potential antitumour function and the underlying mechanisms of CuE in melanoma have not been fully elucidated. Exploration of novel therapeutic targets and their regulators remains essential for the prevention and treatment of melanoma
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