大黄酸诱导肿瘤细胞凋亡及与丝裂霉素的协同作用

RHEIN INDUCES APOPTOSIS IN CANCER CELLS AND SHOWS SYNERGY WITH MITOMYCIN

目的 研究大黄酸 (rhein)诱导肿瘤细胞凋亡及与丝裂霉素 (MMC)的协同作用。方法 采用流式细胞术、琼脂糖凝胶电泳和荧光显微镜观察 ,[3H] 胸苷转运和参入测定 ,MTT法检测。结果 大黄酸可诱导KB细胞凋亡 ,出现sub G1峰与DNA梯形条带。大黄酸与MMC合用能明显提高KB细胞凋亡率。大黄酸可抑制KB细胞核苷转运和DNA合成。大黄酸对KB ,BEL 740 2和MCF 7细胞有一定的增殖抑制作用 ,并且与MMC合用对 3种细胞均有显著协同作用。

AIM To study the apoptosis inducing and growth inhibitory effect of rhein, an herb derived compound, and its combination with mitomycin C (MMC) on cultured tumor cells. METHODS MTT assays were used to determine the inhibition of proliferation by drugs in several tumor cell lines. Nucleoside transport and DNA synthesis inhibition were determined by [ 3H] thymidine transport and incorporation assays. Flow cytometry, electrophoresis on agarose gels and morphological assesment were applied to analyze the apoptotic changes. RESULTS The IC 50 values of nucleoside transport was 19 1 μg·mL -1 and that of the DNA synthesis inhibited by rhein was 27 4 μg·mL -1 . In MTT assay the IC 50 values of rhein for KB, hepatoma BEL 7402 and mammary carcinoma MCF 7 cells were 11 5 μg·mL -1 , 14 0 μg·mL -1 and 18 4 μg·mL -1 respectively. Synergistic effect of rhein and MMC was found in all the three cell lines. As found, rhein induced apoptosis in KB cells, and the increase of apoptotic cells reached 71 0% at 96 h. The combination of rhein and MMC enhanced the induction of apoptosis significantly. CONCLUSION These results suggest that rhein, as a biochemical modulator, might be potentially useful in cancer chemotherapy.