Effects of CD40 ligation combined with chemotherapy drugs on human breast cancer cell lines.
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.


CONCLUSIONS
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.
Department of Emergency Surgery, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu, China.
Zhi-Qing
ZQ
Wang
Jun
J
Wang
Wei-Hua
WH
Ling
Xue-Guang
XG
Zhang
Qin
Q
Shi
D000970:Antineoplastic Agents / Q000494:pharmacology*; D023201:CD40 Ligand / Q000494:pharmacology*; D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D018946:Chemokine CCL5 / Q000235:genetics / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004317:Doxorubicin / Q000494:pharmacology*; D004357:Drug Synergism; D053222:Fas Ligand Protein / Q000235:genetics / Q000378:metabolism; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects*; D006801:Humans; D007371:Interferon-gamma / Q000494:pharmacology*; D012333:RNA, Messenger / Q000235:genetics* / Q000378:metabolism; D047888:Receptors, Tumor Necrosis Factor, Type I / Q000235:genetics / Q000378:metabolism; D011994:Recombinant Proteins / Q000494:pharmacology; D015398:Signal Transduction / Q000187:drug effects; D051028:bcl-2-Associated X Protein / Q000235:genetics / Q000378:metabolism; D051020:bcl-X Protein / Q000235:genetics / Q000378:metabolism
D000970:Antineoplastic Agents; C494826:BAX protein, human; C494811:BCL2L1 protein, human; C483024:CCL5 protein, human; D018946:Chemokine CCL5; D053222:Fas Ligand Protein; D012333:RNA, Messenger; D047888:Receptors, Tumor Necrosis Factor, Type I; D011994:Recombinant Proteins; D051028:bcl-2-Associated X Protein; D051020:bcl-X Protein; D023201:CD40 Ligand; D004317:Doxorubicin; D007371:Interferon-gamma
IFN-γ; anti-tumour; breast cancer cell; doxorubicin; rhCD40L