Expression of housekeeping genes varies depending on mevalonate pathway inhibition in cancer cells

Area of Science:

• Oncology
• Pharmacology
• Molecular Biology

Background:

• Statins exhibit anticancer properties, suggesting their potential for drug repositioning in cancer therapy.
• Accurate gene expression analysis relies on stable internal reference genes, unaffected by experimental conditions.
• Statins inhibit the mevalonate pathway, potentially impacting the expression of housekeeping genes used as reference standards.

Purpose of the Study:

• To evaluate the expression stability of internal reference genes in cancer cell lines treated with atorvastatin.
• To determine if atorvastatin affects housekeeping gene expression in both statin-sensitive and statin-resistant cancer cells.

Main Methods:

• Treatment of statin-sensitive and statin-resistant cancer cell lines with atorvastatin across seven concentrations.
• Performing reverse transcription-quantitative polymerase chain reaction (RT-qPCR) on 15 candidate housekeeping genes.
• Assessing the expression stability of these genes using five distinct algorithms.

Main Results:

• Atorvastatin significantly affected the expression of specific internal reference genes in cancer cell lines.
• The observed effects were dependent on atorvastatin concentration and the specific cancer cell line.
• Expression alterations occurred in both statin-sensitive and statin-resistant cell lines.

Conclusions:

• Caution is necessary when comparing gene expression data between cells treated with statins.
• Validation of internal reference genes is crucial for reliable gene expression analyses in cancer research involving drug treatments.
• Drug repositioning studies using statins require careful consideration of reference gene stability.