Background

Despite the great clinical response to the first-line chemotherapeutics, metastasis still happens among most of the ovarian cancer patients within 2 years.

Methods

Using multiple human ovarian cancer cell lines, a transwell co-culture system of the carboplatin or VP-16-challenged feeder and receptor cells was established to demonstrate the chemotherapy-exacerbated migration. The migration and cancer stem cell (CSC)-like characteristics were determined by wound healing, transwell migration, flow cytometry and sphere formation. mRNA and protein expression were identified by qPCR and western blot. Bioinformatics analysis was used to investigate the differentially expressed genes. GLI1 expression in tissue samples was analysed by immunohistochemistry.

Results

Chemotherapy was found to not only kill tumour cells, but also trigger the induction of CSC-like traits and the migration of ovarian cancer cells. EMT markers Vimentin and Snail in receptor cells were upregulated in the microenvironment of chemotherapy-challenged feeder cells. The transcription factor GLI1 was upregulated by chemotherapy in both clinical samples and cell lines. Follow-up functional experiments illustrated that inhibiting GLI1 reversed the chemotherapy-exacerbated CSC-like traits, including CD44 and CD133, as well as prevented the migration of ovarian cancer cells.

Conclusions

Targeting GLI1 may improve clinical benefits in the chemotherapy-exacerbated metastasis in ovarian cancer treatment.

中文翻译：

---

化疗通过 GLI1 加剧卵巢癌细胞迁移和癌症干细胞样特征。

背景

尽管对一线化疗药物的临床反应很好，但大多数卵巢癌患者在 2 年内仍会发生转移。

方法

使用多种人卵巢癌细胞系，建立了卡铂或 VP-16 攻击的饲养细胞和受体细胞的 transwell 共培养系统，以证明化疗加剧的迁移。迁移和癌症干细胞 (CSC) 样特征通过伤口愈合、transwell 迁移、流式细胞术和球体形成来确定。通过 qPCR 和蛋白质印迹鉴定 mRNA 和蛋白质表达。生物信息学分析用于研究差异表达的基因。通过免疫组织化学分析组织样本中的 GLI1 表达。

结果

化疗不仅可以杀死肿瘤细胞，还可以引发 CSC 样特征的诱导和卵巢癌细胞的迁移。受体细胞中的 EMT 标记波形蛋白和 Snail 在化疗挑战的饲养细胞的微环境中被上调。转录因子 GLI1 在临床样本和细胞系中都被化疗上调。后续功能实验表明，抑制 GLI1 可逆转化疗加剧的 CSC 样特征，包括 CD44 和 CD133，并阻止卵巢癌细胞的迁移。

结论

靶向 GLI1 可能会改善卵巢癌治疗中化疗加剧的转移的临床益处。