Published in Cancer Detection and Prevention 2000; 24(Supplement 1).

Retinoic acid promotes differentiation and enhances chemosensitivity of medulloblastoma cells

J Liu MD PhD, L Guo, L JW Li MD, H Li MD PhD

Div Molecular Biology, Shenyang Medical College, Shenyang, China,

AIM: To elucidate 1) the differentiation potential of medulloblastoma cells and 2) chemosensitivity of Retinoic acid (RA)-differentiated medulloblastoma cells to conventional anticancer reagents and its relevance with the expression patterns of apoptosis-associated genes. METHODS: A comprehensive study was performed on medulloblastoma tumors and cell line Med-3 by multiple approaches of cellular and molecular biology. RESUTS: Leukemia inhibitory factor (LIF) was expressed prevalently in medulloblastoma cells in vivo and in vitro. Blockage of LIF expression or biological activity could inhibit growth and promote Med-3 cells toward differentiation. RA could induce differentiation and down regulate LIF expression and telomerase activity of Med-3 cells. Neither RA nor cisplatin brought about sufficient cell death but their half dose combination could effectively induce apoptosis. FasL molecules in 29kDa and 37kDa were produced in Med-3 cells with and without the treatments. Soluble Fas molecule around 30kDa was found in the normally cultured cells and the cells treated by CP. An additional 45kDa Fas band and the cell surface labeling appeared when the cells had been treated by RA or by RA /CP combination. Anti-Fas antibody could induce apoptosis in the cell population pretreated by RA. CONCLUSIONS: LIF is an autocrinal growth factor for medulloblastomas by inhibiting cell differentiation. RA can enhance chemosensitivity of medulloblastoma Med-3 cells presumably by promoting differentiation and modulating the pattern of Fas expression. The RA/CP combined regimen would be of potential therapeutic value in the treatment of medulloblastomas.

KEY WORDS: retinoic acid, leukemia inhibitory factor, .

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Paper presented at the International Symposium on Impact of Biotechnology on Cancer Diagnostic & Prognostic Indicators; Geneva, Switzerland; October 28 - 31, 2000; in the section on synergistic therapies.