Department of Gynaecology and Obstetrics, Yijishan Hospital of Wannan Medical College, Wuhu, Anhui, China (mainland).
Department of Gynecology and Obstetrics, Yijishan Hospital of Wannan Medical College, Wuhu, Anhui, China (mainland).
Med Sci Monit. 2018 Jun 12;24:3997-4008. doi: 10.12659/MSM.909418.
BACKGROUND Ovarian cancer is a common type of malignant neoplasm. Its prognosis is poor because the disease is not well understood. Abnormal lipometabolism in peroxisomes is involved in tumor progression and hydroxysteroid dehydrogenase-like 2 (HSDL2), localized in peroxisomes, might be a regulatory factor in lipometabolism. However, the role of HSDL2 in ovarian cancer progression remains unknown. MATERIAL AND METHODS HSDL2 expression was detected by qPCR and immunohistochemistry in ovarian tumor samples and qPCR in human ovarian cancer cell lines. Cell proliferation was measured by Celigo and MTT assay. Cell cycle distribution and apoptosis were determined using flow cytometry. Giemsa staining was used for analyzing colony formation. Cell motility was performed using Transwell migration and invasion assays. Tumorigenesis in nude mice was also detected. RESULTS HSDL2 expression was upregulated in human ovarian cancer samples and in 3 human ovarian cancer cell lines: SKOV3, HO8910, and OVCAR-3. Higher expression of HSDL2 in ovarian tumor samples was associated with more progressed tumors (P=0.03) and lymphatic metastases (P=0.03). HSDL2 down-regulation by lentiviral-mediated HSDL2 knockdown suppressed cell proliferation, colony formation, and cell motility, while it promoted cell apoptosis and resulted in cell cycle arrest at the G0/G1 phase in human ovarian cancer cell lines OVCAR-3 and SKOV3. HSDL2 knockdown also inhibited tumorigenesis in mouse models. CONCLUSIONS This study shows that HSDL2 upregulation is associated with ovarian cancer progression. HSDL2 knockdown inhibited cell proliferation, colony formation, motility, and tumorigenesis. It induced apoptosis and cell cycle arrest and might therefore serve as a potential target for ovarian cancer therapy.
卵巢癌是一种常见的恶性肿瘤。由于对该病的认识不足，其预后较差。过氧化物酶体中异常的脂肪代谢与肿瘤进展有关，定位于过氧化物酶体中的羟甾类脱氢酶样 2（HSDL2）可能是脂肪代谢的调节因子。然而，HSDL2 在卵巢癌进展中的作用尚不清楚。
采用 qPCR 和免疫组织化学法检测卵巢肿瘤组织中 HSDL2 的表达，采用 qPCR 法检测人卵巢癌细胞系中 HSDL2 的表达。通过 Celigo 和 MTT 法检测细胞增殖。采用流式细胞术检测细胞周期分布和细胞凋亡。采用吉姆萨染色分析集落形成。通过 Transwell 迁移和侵袭实验检测细胞迁移和侵袭。还检测了裸鼠的肿瘤发生情况。
HSDL2 在人卵巢癌样本和 3 个人卵巢癌细胞系（SKOV3、HO8910 和 OVCAR-3）中表达上调。卵巢肿瘤样本中 HSDL2 表达较高与肿瘤进展程度较高（P=0.03）和淋巴转移（P=0.03）相关。慢病毒介导的 HSDL2 敲低抑制了人卵巢癌细胞系 OVCAR-3 和 SKOV3 中的细胞增殖、集落形成和细胞迁移，而促进了细胞凋亡，并导致细胞周期停滞在 G0/G1 期。HSDL2 敲低也抑制了小鼠模型中的肿瘤发生。
本研究表明，HSDL2 的上调与卵巢癌的进展有关。HSDL2 敲低抑制了细胞增殖、集落形成、迁移和肿瘤发生。它诱导细胞凋亡和细胞周期停滞，因此可能成为卵巢癌治疗的潜在靶点。
