Activation of hedgehog signaling and its association with cisplatin resistance in ovarian epithelial tumors

Song,Xueling; Yan,Liying; Lu,Cuiling; Zhang,Chunyu; Zhu,Fuli; Yang,Jingjing; Jing,Hongyan; Zhang,Yang; Qiao,Jie; Guo,Hongyan

doi:10.3892/ol.2018.8008

Activation of hedgehog signaling and its association with cisplatin resistance in ovarian epithelial tumors

Authors:
- Xueling Song
- Liying Yan
- Cuiling Lu
- Chunyu Zhang
- Fuli Zhu
- Jingjing Yang
- Hongyan Jing
- Yang Zhang
- Jie Qiao
- Hongyan Guo
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Affiliations: Department of OB/GYN, Peking University Third Hospital, Beijing 100191, P.R. China
Published online on: February 9, 2018 https://doi.org/10.3892/ol.2018.8008
Pages: 5569-5576
Copyright: © Song et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Few studies have evaluated Hedgehog (Hh) signaling pathway activation in different types of ovarian tumors including benign, borderline and malignant ovarian tumors. The present study investigated the expression of Hh signaling pathway components (SHH, SMO, PTCH, and GLI1) in 193 ovarian epithelial tumor specimens (including 147 malignant epithelial ovarian cancers, 30 borderline ovarian tumors, 16 benign ovarian epithelial tumors) and 11 normal ovarian epithelial tissues by immunohistochemistry. The results demonstrated widespread expression of Hh pathway molecules in ovarian tumors. However, there was no significant difference in the expression intensity of SHH among the four groups (P>0.05). Statistically significant differences were identified in the expression intensity of the SMO, PICH and GLI1 among groups (P<0.001). In addition, significant differences were also revealed in the expression levels of SMO (P=0.013) and GLI1 (P=0.0005) between the platinum drug‑sensitive and drug‑resistant groups. The overexpression of SMO and GLI1 was further confirmed in the cisplatin‑resistant ovarian cancer cell line A2780/DDP by immunoﬂuorescence, flow cytometry and western blotting. The results revealed that the Hh pathway components SMO, PICH and GLI1 are activated in ovarian epithelial tumors. Novel potential associations between cisplatin resistance and the overexpression of SMO and Gli1 in malignant epithelial ovarian cancer were also observed, which may provide an innovative approach to the treatment of drug resistant ovarian epithelial cancer.

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