Inhibition-of-BUB1-Kinase-by-BAY-1816032-Sensitizes-Tumor-Cells-toward-Taxanes-ATR-and-PARP-Inhibitors-In-Vitro-and-In-Vivo

by Selleckchem | Sep 11 2023

Osteosarcoma (OS) is a primary malignant bone tumour that mainly affects teenagers, with patients displaying poor prognosis. Budding uninhibited by benzimidazoles 1 (BUB1), a type of serine/threonine kinase that is linked to pro-tumorigenic phenomena, has not been well studied in OS. Hence, this study aimed to explore the role of BUB1 in OS. The expression of BUB1 in OS specimens and cell lines was assessed using immunohistochemistry and Western blot analysis. Univariate and multivariate analyses were applied to evaluate the impact of BUB1 on patient survival. Cell counting kit-8, wound-healing and Transwell assays, as well as flow cytometry, were used to investigate the influence of BUB1 inhibition on OS in vitro. Moreover, a tumour xenograft model was established to investigate the in vivo effect of BUB1 inhibition on OS tumour growth. Results showed that BUB1 was overexpressed in OS specimens and cell lines. Furthermore, BUB1 overexpression was closely associated with the poor clinical outcomes of patients with OS. Inhibition of BUB1 markedly suppressed cell proliferation and tumour growth, cell migration, invasion and induced cell apoptosis of OS by blocking the PI3K/Akt and ERK signalling pathways. Thus, our study suggested that overexpression of BUB1 protein contributed to poor survival of OS patients and that inhibition of BUB1 resulted in considerable anti-tumour activity associated with proliferation, migration, invasion and apoptosis of OS.

Comments:

The study you described aimed to investigate the role of BUB1 (budding uninhibited by benzimidazoles 1), a type of serine/threonine kinase, in osteosarcoma (OS), a primary malignant bone tumor that primarily affects teenagers and has a poor prognosis. Here is a summary of the key findings and methods used in the study:

1. Expression of BUB1: The researchers assessed the expression of BUB1 in OS specimens and cell lines using immunohistochemistry and Western blot analysis. The results showed that BUB1 was overexpressed in both OS specimens and cell lines.

2. Clinical impact: The study evaluated the impact of BUB1 expression on patient survival using univariate and multivariate analyses. The findings indicated that BUB1 overexpression was closely associated with poor clinical outcomes in OS patients.

3. In vitro experiments: To investigate the influence of BUB1 inhibition on OS, the researchers conducted several in vitro assays. These included the cell counting kit-8 assay to assess cell proliferation, wound-healing and Transwell assays to measure cell migration and invasion, and flow cytometry to evaluate apoptosis. Inhibition of BUB1 resulted in significant suppression of cell proliferation, migration, invasion, and induction of apoptosis in OS cells.

4. Signaling pathways: The study explored the underlying mechanisms of BUB1's effects in OS. The inhibition of BUB1 was found to block the PI3K/Akt and ERK signaling pathways, which are known to be involved in cell proliferation and survival.

5. In vivo experiments: The researchers established a tumor xenograft model to investigate the in vivo effect of BUB1 inhibition on OS tumor growth. The results demonstrated that inhibiting BUB1 had a considerable anti-tumor activity, further supporting its potential as a therapeutic target for OS.

In conclusion, the study provided evidence that BUB1 overexpression is associated with poor survival in OS patients. Inhibition of BUB1 showed significant anti-tumor activity by suppressing cell proliferation, migration, invasion, and promoting apoptosis in OS cells. The study suggests that BUB1 may serve as a potential therapeutic target for OS treatment.