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Published on: January 12, 2020
The Sonic Hedgehog signaling pathway regulates autophagy and migration in ovarian cancer
Yibin Pan1,2, Jiena Zhou1,2,3, Weidan Zhang1,2,4
1Assisted Reproduction Unit, Department of Obstetrics and Gynecology, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Zhejiang University, Hangzhou, China.
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.
Insights
In epithelial ovarian cancer, Sonic Hedgehog (SHH) pathway is upregulated, promoting cell migration. Inhibiting SHH and autophagy may offer a new therapeutic strategy for ovarian cancer treatment.
Area of Science:
- Oncology
- Molecular Biology
- Cell Signaling
Background:
- The Sonic Hedgehog (SHH) signaling pathway is implicated in human cancers, but its precise role in ovarian cancer remains unclear.
- Understanding SHH pathway mechanisms is crucial for developing targeted ovarian cancer therapies.
Purpose of the Study:
- To investigate the role of the SHH signaling pathway and autophagy in epithelial ovarian cancer (EOC).
- To explore the therapeutic potential of inhibiting the SHH pathway and autophagy in EOC.
Main Methods:
- Expression analysis of SHH and SQSTM1 in ovarian tumor tissues.
- In vitro and in vivo experiments using SHH inhibitor (Cyclopamine) and autophagy inhibitor (chloroquine).
- Assays included autophagic flux, cell viability (CCK-8), migration (wound healing, Transwell), and tumor xenografts. Mechanistic studies utilized qRT-PCR and Western Blot.
Main Results:
- SHH and SQSTM1/P62 were upregulated in epithelial ovarian cancer tissues.
- Cyclopamine induced autophagy via the PI3K/AKT pathway.
- Combined low-dose Cyclopamine and chloroquine enhanced SKOV3 cell migration.
Conclusions:
- SHH pathway inhibition and autophagy modulation show promise as a therapeutic strategy for ovarian cancer.
- Targeting both SHH signaling and autophagy may represent a novel approach for EOC treatment.
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