The Sonic Hedgehog signaling pathway regulates autophagy and migration in ovarian cancer
Abstract 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...
| Main Authors: | , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Wiley
2021-07-01
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| Series: | Cancer Medicine |
| Subjects: | |
| Online Access: | https://doi.org/10.1002/cam4.4018 |
| _version_ | 1818847221996584960 |
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| author | Yibin Pan Jiena Zhou Weidan Zhang Lili Yan Meifei Lu Yongdong Dai Hanjing Zhou Songying Zhang Jianhua Yang |
| author_facet | Yibin Pan Jiena Zhou Weidan Zhang Lili Yan Meifei Lu Yongdong Dai Hanjing Zhou Songying Zhang Jianhua Yang |
| author_sort | Yibin Pan |
| collection | DOAJ |
| description | Abstract 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. |
| first_indexed | 2024-12-19T05:58:01Z |
| format | Article |
| id | doaj.art-5ae218ec7ab24ad98c4647537ecb2d4c |
| institution | Directory Open Access Journal |
| issn | 2045-7634 |
| language | English |
| last_indexed | 2024-12-19T05:58:01Z |
| publishDate | 2021-07-01 |
| publisher | Wiley |
| record_format | Article |
| series | Cancer Medicine |
| spelling | doaj.art-5ae218ec7ab24ad98c4647537ecb2d4c2022-12-21T20:33:23ZengWileyCancer Medicine2045-76342021-07-0110134510452110.1002/cam4.4018The Sonic Hedgehog signaling pathway regulates autophagy and migration in ovarian cancerYibin Pan0Jiena Zhou1Weidan Zhang2Lili Yan3Meifei Lu4Yongdong Dai5Hanjing Zhou6Songying Zhang7Jianhua Yang8Assisted Reproduction Unit Department of Obstetrics and Gynecology Sir Run Run Shaw HospitalZhejiang University School of MedicineZhejiang University Hangzhou ChinaAssisted Reproduction Unit Department of Obstetrics and Gynecology Sir Run Run Shaw HospitalZhejiang University School of MedicineZhejiang University Hangzhou ChinaAssisted Reproduction Unit Department of Obstetrics and Gynecology Sir Run Run Shaw HospitalZhejiang University School of MedicineZhejiang University Hangzhou ChinaAssisted Reproduction Unit Department of Obstetrics and Gynecology Sir Run Run Shaw HospitalZhejiang University School of MedicineZhejiang University Hangzhou ChinaDepartment of Pharmacy The Children's HospitalZhejiang University School of MedicineNational Clinical Research Center for Child Health Hangzhou Zhejiang Province ChinaAssisted Reproduction Unit Department of Obstetrics and Gynecology Sir Run Run Shaw HospitalZhejiang University School of MedicineZhejiang University Hangzhou ChinaAssisted Reproduction Unit Department of Obstetrics and Gynecology Sir Run Run Shaw HospitalZhejiang University School of MedicineZhejiang University Hangzhou ChinaAssisted Reproduction Unit Department of Obstetrics and Gynecology Sir Run Run Shaw HospitalZhejiang University School of MedicineZhejiang University Hangzhou ChinaAssisted Reproduction Unit Department of Obstetrics and Gynecology Sir Run Run Shaw HospitalZhejiang University School of MedicineZhejiang University Hangzhou ChinaAbstract 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.https://doi.org/10.1002/cam4.4018autophagychloroquinecyclopaminemigrationsonic hedgehog pathwayxenografts |
| spellingShingle | Yibin Pan Jiena Zhou Weidan Zhang Lili Yan Meifei Lu Yongdong Dai Hanjing Zhou Songying Zhang Jianhua Yang The Sonic Hedgehog signaling pathway regulates autophagy and migration in ovarian cancer Cancer Medicine autophagy chloroquine cyclopamine migration sonic hedgehog pathway xenografts |
| title | The Sonic Hedgehog signaling pathway regulates autophagy and migration in ovarian cancer |
| title_full | The Sonic Hedgehog signaling pathway regulates autophagy and migration in ovarian cancer |
| title_fullStr | The Sonic Hedgehog signaling pathway regulates autophagy and migration in ovarian cancer |
| title_full_unstemmed | The Sonic Hedgehog signaling pathway regulates autophagy and migration in ovarian cancer |
| title_short | The Sonic Hedgehog signaling pathway regulates autophagy and migration in ovarian cancer |
| title_sort | sonic hedgehog signaling pathway regulates autophagy and migration in ovarian cancer |
| topic | autophagy chloroquine cyclopamine migration sonic hedgehog pathway xenografts |
| url | https://doi.org/10.1002/cam4.4018 |
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