The Journal of international medical research · 2013
Effects of CD40 ligation combined with chemotherapy drugs on human breast cancer cell lines.
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Wang Zhi-Qing, Wang Jun, Ling Wei-Hua, Zhang Xue-Guang, Shi Qin
Аннотация
OBJECTIVE: To investigate the influence of recombinant human CD40 ligand (rhCD40L) on the biological behaviour of breast cancer cells.
METHODS: MDA-MB-23l and MDA-MB-435 treated with rhCD40L were observed for changes in the cell cycle, in membrane proteins, and in mRNA levels of B cell lymphoma-extra-large (Bcl-xl), Bcl-2 associated X protein (Bax) and regulated upon activation, normal T cell expressed and secreted (RANTES). Effects of rhCD40L on cell proliferation in the presence or absence of interferon (IFN)-γ (500 IU/ml) and/or doxorubicin (20 ng/ml) were also determined.
RESULTS: rhCD40L dose-dependently inhibited cell proliferation. Combination of rhCD40L with IFN-γ or doxorubicin potentiated the inhibitory activity. After treatment, an increase in cells entering the G₁ phase of the cell cycle was observed, with a significant decrease in the number entering the S phase. Levels of several membrane proteins including CD95L and CD120a were also increased. Reverse transcription-polymerase chain reaction revealed an increase in the Bax/Bcl-xl mRNA ratio and an increase in RANTES.
CONCLUSION: rhCD40L treatment of breast cancer cells mediates a variety of anti-tumour effects, not only by direct cytotoxic activity but also by upregulation of adhesion molecules, co-stimulators and cytokines to rectify T cell immunity.
METHODS: MDA-MB-23l and MDA-MB-435 treated with rhCD40L were observed for changes in the cell cycle, in membrane proteins, and in mRNA levels of B cell lymphoma-extra-large (Bcl-xl), Bcl-2 associated X protein (Bax) and regulated upon activation, normal T cell expressed and secreted (RANTES). Effects of rhCD40L on cell proliferation in the presence or absence of interferon (IFN)-γ (500 IU/ml) and/or doxorubicin (20 ng/ml) were also determined.
RESULTS: rhCD40L dose-dependently inhibited cell proliferation. Combination of rhCD40L with IFN-γ or doxorubicin potentiated the inhibitory activity. After treatment, an increase in cells entering the G₁ phase of the cell cycle was observed, with a significant decrease in the number entering the S phase. Levels of several membrane proteins including CD95L and CD120a were also increased. Reverse transcription-polymerase chain reaction revealed an increase in the Bax/Bcl-xl mRNA ratio and an increase in RANTES.
CONCLUSION: rhCD40L treatment of breast cancer cells mediates a variety of anti-tumour effects, not only by direct cytotoxic activity but also by upregulation of adhesion molecules, co-stimulators and cytokines to rectify T cell immunity.
Предметные рубрики MeSH
Antineoplastic AgentsCD40 LigandCell CycleCell Line, TumorCell ProliferationChemokine CCL5Dose-Response Relationship, DrugDoxorubicinDrug SynergismFas Ligand ProteinFemaleGene Expression Regulation, NeoplasticHumansInterferon-gammaRNA, MessengerReceptors, Tumor Necrosis Factor, Type IRecombinant ProteinsSignal Transductionbcl-2-Associated X Proteinbcl-X Protein