2000 Fiscal Year Final Research Report Summary
"INHIBITION OF HUMAN BREAST CARCINOMA GROWTH BY A SOLUBLE RECOMBINANT HUMAN CD40 LIGAND"
| Project/Area Number |
11671189
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
General surgery
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| Research Institution | JIKEI UNIVERSITY SCHOOL OF MEDICINE |
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Principal Investigator |
HIRANO Akio M.D., DEPARTMENT OF INTERNAL MEDICINE, SENIOR INVESTIGATOR, 医学部, 助手 (80307462)
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| Project Period (FY) |
1999 – 2000
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| Keywords | CD40 / CD40ligand (srhCD40L) / human brest cancer / SCID mouse / interferon-γ / apoptosis |
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| Research Abstract |
1. Surface expression of CD40 on human breast cancer cell line.Immunofluorescence studies were performed by flow cytometric analysis. CD40 was expressed on various human breast cancer cell lines, MDA-231, T-47D, and BT20.
2. Induction of CD40 expression by interferon-γ in vitro Incubation with interferon-γ significantly induced surface expression on human brest cancer cell lines.
3. Antitumor effects of soluble recombinant human CD40 ligand (srhCD40L) and interferon-γ on human brest cancer cell lines in vitro. Incubation with srhCD40L significantly inhibited the proliferation of MDA-231 and T-47D as determined by the proliferation assay with optimal inhibition of MTT assay. Apoptotic studies by flow cytometry revealed an induction of apoptosis in these two cell lines. Additional inhibitory effect by co-incubation with interfron-γ significantly enhanced this inhibitory effects.
4. Antitumor effects of srhCD40L treatment in SCID mice bearing human human brest cancer cell lines. Effects of srhCD40L treatment on survival in human brest cancer cell-bearing SCID mice were determined. All mice received 20 μL of anti-asialo GM1 (Wako Chemicals, Osaka) by intravenous injection (IV) 1 day before tumor transfer to remove host natural killer cells. MDA-231 cells (5×10^6) were then administered by IV.SCID recipients then received either 10 μg of srhCD40L or control every other day for 20 days for total of 10 injections starting at day 3. Tumor bearing mice were then monitored for tumor development and progression. Treatment with srhCD40L significantly improved the survival of tumor-bearing mice (p<0.05).
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