[Effects of fludarabine on apoptosis and gene expression profile in multiple myeloma cells]
Chun-Mei Yang1, Hai-Tao Meng, Hui Liu
1The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou 310003, China.
Objective:
To investigate the in vitro effects of fludarabine on apoptosis and gene expression profile in human multiple myeloma (MM) cells.
Methods:
Cell growth was measured by a MTT assay. Cells apoptosis was evaluated by flow cytometry. The activation of caspase cascade was determined by Western blot analysis. The expression profile of apoptosis-related genes in human MM cells was detected by cDNA expression array system.
Results:
The growth of RPMI8226 and KM3 cells was suppressed by fludarabine treatment in a dose and time-dependent manner. After treatment with fludarabine for 24 h, the IC(50) for RPMI8226 cells was 2.13 µg/ml, and 0.36 µg/ml for KM3 cells. Apoptotic cells of RPMI8226 and KM3 increased in a dose- dependent manner after exposure to fludarabine for 24 h. Western blot analysis showed the activation of caspase-3 and PARP in the MM cells treated with fludarabine. The cDNA expression array showed that multiple pathways were involved in the apoptosis induced by fludarabine. Among 97 apoptosis-related genes, 25 genes were differently expressed and 13 expressions were up-regulated in fludarabine treated group, involving in Bcl-2 pro-apoptotic gene, tumor necrosis factor (TNF) and its receptor superfamily gene, and caspase recruitment domain family, 12 genes expression down-regulated, including Bcl-2 antiapoptotic gene, TNF superfamily and its receptor related factor gene and apoptosis inhibitor protein family.
Conclusion:
Fludarabine can significantly inhibit MM cell growth and induce apoptosis in vitro. The multiple pathways may be involved for the apoptosis in MM cells.
Insights
Fludarabine effectively inhibits human multiple myeloma (MM) cell growth and induces apoptosis in vitro. Gene expression analysis reveals fludarabine impacts multiple apoptosis-related pathways, offering insights into MM treatment strategies.
Area of Science:
- Oncology
- Molecular Biology
- Pharmacology
Background:
- Multiple myeloma (MM) is a hematological malignancy characterized by uncontrolled proliferation of plasma cells.
- Understanding the molecular mechanisms of MM cell death is crucial for developing targeted therapies.
Purpose of the Study:
- To investigate the in vitro effects of fludarabine on apoptosis and gene expression in human multiple myeloma (MM) cells.
- To elucidate the molecular pathways involved in fludarabine-induced apoptosis in MM.
Main Methods:
- Cell viability assessed using MTT assay.
- Apoptosis evaluated by flow cytometry.
- Caspase cascade activation determined by Western blot.
- Apoptosis-related gene expression profiled using cDNA expression array.
Main Results:
- Fludarabine suppressed RPMI8226 and KM3 cell growth in a dose- and time-dependent manner.
- Fludarabine treatment increased apoptosis and activated caspase-3 and PARP.
- Differential expression of 25 apoptosis-related genes, including those in Bcl-2, TNF, and caspase recruitment domain families, was observed.
Conclusions:
- Fludarabine demonstrates significant in vitro efficacy in inhibiting MM cell growth and inducing apoptosis.
- Multiple molecular pathways are implicated in fludarabine-induced apoptosis in MM cells.
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