Objective:

To investigate the role of Polo-like kinase 1 (PLK1) in colorectal cancer (CRC) and the effects of nitidine chloride (NC) on PLK1 expression, specifically hypothesizing that NC may inhibit PLK1 and affect CRC progression.

Key Findings:

• PLK1 is overexpressed in CRC and identified as a prominent NC-responsive gene, suggesting its potential as a therapeutic target.
• NC treatment significantly reduced PLK1 expression at both mRNA and protein levels, indicating a direct effect on PLK1 regulation.
• MYCN was downregulated after NC treatment, suggesting a potential regulatory relationship with PLK1 that may influence CRC treatment outcomes.

Interpretation:

The findings suggest that NC may exert its anti-cancer effects in CRC by targeting PLK1 through MYCN-related transcriptional mechanisms, indicating a novel therapeutic pathway.

Limitations:

• The study primarily focuses on in vitro and in vivo models, which may not fully replicate human CRC complexity, potentially limiting the generalizability of the results.
• Further clinical validation is needed to confirm the therapeutic potential of NC in CRC, addressing potential biases in model systems.

Conclusion:

This study highlights PLK1 as a critical target of NC in CRC and suggests that the MYCN–PLK1 axis may be a key regulatory component in the anti-CRC effects of NC, paving the way for future therapeutic strategies.