目的 研究葡聚糖衍生物对乳腺癌的作用。方法以肝素表达缺陷而稳定表达成纤维细胞生长因子受体(FGFR)的F32细胞系和乳腺癌细胞系MCF-7、MCF-7ras为模型,利用3H—thymidine摄入技术,研究人工合成的葡聚糖衍生物对细胞生长的影响,并初步探讨其作用机制。结果葡聚糖衍生物能够有效作用于HS/FGF/FGFR复合物,但对两种乳腺癌细胞系具有完全相反的两种作用,即刺激MCF-7的生长而对MCF-7ras则抑制生长。构效研究发现,磺酸基团和苯环是影响葡聚糖衍生物活性重要基团。结论葡聚糖衍生物与肝素具有相似的性质,对细胞生长具有双重性。
Objective To study the effect of dextran derivatives on breast cancer cells. Methods Human breast cancer cell lines MCF-7 and MCF-7ras as well as F32 cell llne, which is defective in heparin expression but expresses FGFR steadily , were used in the study. The effect of synthetic dextran derivatives on the growth of the cells was studied with the 3 Hthymidine incorporation technique. The mechanisms underlying the effect were tentatively approached. Results The synthetic dextran derivatives were shown to modulate the cell proliferation of the F32 cell line by interacting with the HS/FGF/FCFR complex on the cell surface. These dextran derivatives, however, showed completely opposite effects on the 2 human breast cancer cell lines, stimulating the DNA synthesis of the MCF-7 cells while inhibiting that of the MCF-7ras cells. Structure-activity study revealed that sulfonate and benzene ring are the important chemical groups influencing the biological activity of the dextran derivatives. Conclusion Dextran derivatives were shown to be provided with a quality similar to that of heparin in that they show dual effects on cell proliferation.