Assisted Reproduction Unit, Department of Obstetrics and Gynecology, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Zhejiang University, Hangzhou, China.
Key Laboratory of Reproductive Dysfunction Management of Zhejiang Province, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Zhejiang University, Hangzhou, China.
Cancer Med. 2021 Jul;10(13):4510-4521. doi: 10.1002/cam4.4018. Epub 2021 Jun 2.
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.
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.
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.
Our findings suggest that inhibition of the SHH pathway and autophagy may be a potential and effective therapy for the treatment of ovarian cancer.
Sonic Hedgehog（SHH）信号通路在包括卵巢癌在内的多种人类癌症中发挥着重要作用；然而，其在卵巢癌中的功能和潜在机制仍不完全清楚。
我们检测了交界性卵巢肿瘤组织、上皮性卵巢癌（EOC）组织和良性卵巢肿瘤组织中 SHH 和 SQSTM1 的表达。使用环巴胺（Cyp，SHH 信号通路的著名抑制剂）和氯喹（CQ，自噬的药物抑制剂）进行体内和体外实验（自噬流、CCK-8 测定、划痕愈合试验、Transwell 测定、肿瘤异种移植模型）。通过定量 RT-PCR 和 Western Blot 探索其作用机制。
我们发现上皮性卵巢癌中 SHH 上调和 SQSTM1/P62 积累。Cyp 通过 PI3K/AKT 信号通路诱导自噬。此外，低剂量 Cyp 和氯喹（CQ）显著促进了 SKOV3 细胞的迁移能力。
我们的研究结果表明，抑制 SHH 通路和自噬可能是治疗卵巢癌的一种有潜力和有效的治疗方法。
