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The Sonic Hedgehog signaling pathway regulates autophagy and migration in ovarian cancer
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The Sonic Hedgehog signaling pathway regulates autophagy and migration in ovarian cancer
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Journal Article
The Sonic Hedgehog signaling pathway regulates autophagy and migration in ovarian cancer
2021
Overview
Background The Sonic Hedgehog (SHH) signaling pathway plays an important role in various types of human cancers including ovarian cancer; however, its function and underlying mechanism in ovarian cancer are still not entirely understood. Methods We detected the expressions of SHH and SQSTM1 in borderline ovarian tumor tissues, epithelial ovarian cancer (EOC) tissues and benign ovarian tumor tissues. Cyclopamine (Cyp, a well‐known inhibitor of SHH signaling pathway) and chloroquine (CQ, the pharmaceutical inhibitor of autophagy) were used in vivo and in vitro (autophagic flux, CCK‐8 assay, wound healing assay, transwell assay, tumor xenograft model). The mechanism of action was explored through Quantitative RT‐PCR and Western Blot. Results We found up‐regulation of SHH and accumulation of SQSTM1/P62 in epithelial ovarian cancer. Cyp induced autophagy through the PI3K/AKT signaling pathway. Moreover, low‐dose Cyp and chloroquine (CQ) significantly promoted the migratory ability of SKOV3 cells. Conclusions Our findings suggest that inhibition of the SHH pathway and autophagy may be a potential and effective therapy for the treatment of ovarian cancer. In this manuscript, we show that SHH signaling was active in ovarian cancer tissues. Inhibition of SHH signaling by cyclopamine (Cyp) enhanced the autophagy and promoted autophagic flux in ovarian cancer cell lines through PI3K/AKT signaling pathway. Our findings provided the experimental basis for simultaneously inhibiting the SHH pathway and autophagy as a new effective therapeutic strategy for patients with ovarian cancer.
Publisher
John Wiley & Sons, Inc,John Wiley and Sons Inc,Wiley
Subject
1-Phosphatidylinositol 3-kinase
/ Animals
/ Autophagic Cell Death - drug effects
/ Autophagic Cell Death - physiology
/ Carcinoma, Ovarian Epithelial - metabolism
/ Carcinoma, Ovarian Epithelial - pathology
/ Dosage
/ Female
/ Hedgehog Proteins - antagonists & inhibitors
/ Hedgehog Proteins - metabolism
/ Humans
/ Mice
/ Ovarian Neoplasms - metabolism
/ Ovarian Neoplasms - pathology
/ Patients
/ Phosphatidylinositol 3-Kinases - metabolism
/ Proto-Oncogene Proteins c-akt - metabolism
/ RNA-Binding Proteins - metabolism
/ Sequestosome-1 Protein - metabolism
