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.
OBJECTIVE: To investigate the influence of recombinant humanCD40 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.
Entities:
Keywords:
IFN-γ; anti-tumour; breast cancer cell; doxorubicin; rhCD40L