The Sonic Hedgehog signaling pathway regulates autophagy and migration in ovarian cancer

作者：Yibin Pan, Jiena Zhou, Weidan Zhang, Lili Yan, Meifei Lu, Yongdong Dai, Hanjing Zhou, Songying Zhang, Jianhua Yang · 发表于：Cancer Medicine · 年份：2021 · DOI：10.1002/cam4.4018 · 被引用次数：18 · 研究领域：Hedgehog Signaling Pathway Studies、Autophagy in Disease and Therapy、Cancer, Stress, Anesthesia, and Immune Response

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.