A novel time-course cDNA microarray analysis method identifies genes associated with the development of cisplatin resistance
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Updated: Aug 8, 2026
Evaluating the Effectiveness of Cancer Drug Sensitization In Vitro and In Vivo
Published on: February 6, 2015
Martin A Whiteside1, Dung-Tsa Chen, Renee A Desmond
1Cancer Prevention Fellowship Program, Division of Cancer Prevention, National Cancer Institute, Bethesda, MD, USA.
Abstract:
In recent years, most cDNA microarray studies of chemotherapeutic drug resistance have not considered the temporal pattern of gene expression. The objective of this study was to examine systematically changes in gene expression of NCI-H226 and NCI-H2170 lung cancer cells treated weekly with IC10 doses of cisplatin. NCI-H226 lung cancer cells were treated weekly with an IC10 dose of cisplatin. Candidate genes with a fold change of 2.0 or more were identified from this study. A second experiment was conducted by exposing NCI-H2170 cells to cisplatin doses that were increased in week 4 and decreased in week 5. Overall, 44 genes were differentially expressed in both the NCI-H226 and NCI-H2170 cell lines. In the NCI-H2170 cell line, 24 genes had a twofold gene expression change from weeks 3 to 4. Real-time PCR found a significant correlation of the gene expression changes for seven genes of interest. This small time-ordered series identified novel genes associated with cisplatin resistance. This kind of analysis should be viewed as a first step towards building gene-regulatory networks.
Insights
This study analyzed gene expression changes in lung cancer cells treated with cisplatin, identifying novel genes linked to drug resistance. The findings offer a foundation for understanding gene regulatory networks in chemotherapy.
Area of Science:
- Molecular Biology
- Genomics
- Cancer Research
Background:
- Chemotherapeutic drug resistance is a major challenge in cancer treatment.
- Most studies overlook the dynamic, temporal patterns of gene expression during drug resistance development.
- Understanding these temporal changes is crucial for developing effective cancer therapies.
Purpose of the Study:
- To systematically examine gene expression changes in NCI-H226 and NCI-H2170 lung cancer cells treated with cisplatin over time.
- To identify candidate genes associated with cisplatin resistance using a temporal gene expression analysis.
- To lay the groundwork for constructing gene-regulatory networks involved in drug resistance.
Main Methods:
- Treatment of NCI-H226 lung cancer cells with weekly IC10 doses of cisplatin.
- Exposure of NCI-H2170 cells to varying cisplatin doses over several weeks.
- Identification of differentially expressed genes with a fold change of 2.0 or more.
- Validation of gene expression changes using real-time polymerase chain reaction (PCR).
Main Results:
- 44 genes were found to be differentially expressed in both NCI-H226 and NCI-H2170 cell lines.
- In NCI-H2170 cells, 24 genes showed a twofold change in expression between weeks 3 and 4.
- Real-time PCR confirmed significant expression changes for seven key genes of interest.
- This time-ordered analysis identified novel genes associated with cisplatin resistance.
Conclusions:
- Temporal gene expression analysis is a valuable approach for identifying genes involved in chemotherapy resistance.
- The study identified novel candidate genes contributing to cisplatin resistance in lung cancer.
- These findings represent a crucial first step towards elucidating gene-regulatory networks in drug resistance.
