[Screening the Drug Sensitivity Genes Related to GEM and CDDP in the Lung Cancer Cell-lines.]
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Published on: January 7, 2019
Chunyu Yang1, Zhennan Tian, Wei Liu
1Department of Medical Oncology, the Third Affiliated Hospital of Harbin Medical University, Harbin 150040, China.
Background:
Background and objective Screening of small-cell lung cancer (SCLC) and non-small cell lung cancer (NSCLC) cell lines with gemcitabine hydrochloride (GEM) and cisplatin (CDDP) related to drug sensitivity gene might clarify the action mechanism of anti-cancer drugs and provide a new clue for overcoming drug resistance and the development of new anti-cancer drugs, and also provide theoretical basis for the clinical treatment of individual.
Methods:
The drug sensitivity of CDDP and GEM in 4 SCLC cell lines and 6 NSCLC cell lines was determined using MTT colorimetric assay, while the cDNA macroarray was applied to detect the gene expression state related to drug sensitivity of 10 lung cancer cell line in 1 291, and the correlation between the two was analysized.
Results:
There were 6 genes showing significant positive correlation (r>=0.632, P<0.05) with GEM sensitivity; 45 genes positively related to CDDP; another 41 genes related to both GEM and CDDP (r>=+/- 0.4). Lung cancer with GEM and CDDP sensitivity of two types of drugs significantly related genes were Metallothinein (Signal transduction molecules), Cathepsin B (Organization protease B) and TIMP1 (Growth factor); the GEM, CDDP sensitivity associated genes of lung cancer cell lines mainly distributed in Metallothinein, Cathepsin B, growth factor TIMP1 categories.
Conclusions:
There existed drug-related sensitive genes of GEM, CDDP in SCLC and NSCLC cell lines; of these genes, Metallothinein, Cathepsin B and TIMP1 genes presented a significant positive correlation with GEM drug sensitivity, a significant negative correlation with CDDP drug sensitivity.
Insights
Researchers identified key genes linked to gemcitabine and cisplatin sensitivity in lung cancer. Metallothinein, Cathepsin B, and TIMP1 show distinct correlations with these anti-cancer drug responses.
Area of Science:
- Oncology
- Molecular Biology
- Pharmacogenomics
Context:
- Small-cell lung cancer (SCLC) and non-small cell lung cancer (NSCLC) pose significant therapeutic challenges.
- Drug resistance to standard chemotherapies like gemcitabine (GEM) and cisplatin (CDDP) limits treatment efficacy.
- Understanding the genetic basis of drug sensitivity is crucial for personalized cancer therapy.
Purpose:
- To investigate the relationship between gene expression and sensitivity to GEM and CDDP in lung cancer cell lines.
- To identify specific genes that correlate with the efficacy of these chemotherapeutic agents.
- To provide a foundation for developing novel strategies to overcome drug resistance in lung cancer.
Summary:
- Drug sensitivity assays (MTT) and cDNA macroarray analysis were performed on 10 lung cancer cell lines (4 SCLC, 6 NSCLC).
- Significant correlations were found between gene expression and sensitivity to GEM (6 genes) and CDDP (45 genes).
- Metallothinein, Cathepsin B, and TIMP1 were identified as key genes associated with both GEM and CDDP sensitivity, exhibiting differential correlation patterns.
Impact:
- Identifies potential biomarkers for predicting response to GEM and CDDP in lung cancer patients.
- Offers insights into the molecular mechanisms underlying chemoresistance.
- May guide the development of new therapeutic strategies and combination therapies for lung cancer.