Role of OCT4 in cisplatin treatment of testicular embryonal carcinoma
Purpose: To determine the role of embryonal transcription factor OCT4 in cisplatin treatment of testicular embryonal carcinoma.
Methods: In vitro assays were employed to assess the effect of cisplatin treatment on testicular embryonal carcinoma cell lines under OCT4 silencing. Following treatment with 500 ng/μL cisplatin, MTT assay was used to examine cell proliferation of 2012-EP and 833K-E cells with or without OCT silencing, while wound healing assay was used to examine cell migration ability. Transwell assay and crystal violet staining were employed to measure cell invasive capacity, whereas the distribution pattern of cell cycle was assessed by flow cytometry. The expression levels of several critical components in tumorigenicity related pathways with or without OCT silencing were determined by Western-blot analysis.
Results: Cisplatin enhanced OCT4-silenced cell viability at all concentration (p < 0.01) when compared to control cells. Upon treatment with 500 ng/μL cisplatin, OCT4-silenced cells showed 2- to 3-fold enhancement in cell proliferation (p < 0.001), 2-fold increase in cell migration capacity (p < 0.001), and about 1.5-fold enhancement in invasive capacity (p < 0.001) when compared to control cells. In addition, OCT4 silencing upregulated the expression level of the proteins involved in cell proliferation, cell mobility, cancer metastasis and cell cycle control.
Conclusion: The results suggest that OCT4 may serve as a therapeutic target for testicular embryonal carcinoma treatment in combination with cisplatin by modulating OCT4 expression level. This physiological evidence indicates that OCT4 downregulation contributes to cisplatin resistance in chemotherapy and subsequent disease relapse.
Keywords: OCT4, Cisplatin resistance, Testicular embryonal carcinoma, Chemotherapy