The Anticancer Activity Research On Oridonin

Oridonin was an ent-kaurane diterpenoid which was the most important and potent anticancer constituent of the plant—Rabdosia rubescens. The present research aimed to investigate the anticancer activity and mechanism of Oridonin in vitro and in vivo.In vitro Oridonin inhibited the growth of various cancer cells from kinds of tissues whose IC₅₀ values were all smaller than 20μg·ml^-1 and I_max values were higher than 70%. The human gastric cancer cell BGC823 and murine melanoma cell B16-BL6 were more sensitive to Oridonin than other tested cancer cells. By using FCM assays, we have revealed that Oridonin induced G2/M phase arrest of the BGC823 cells and reduced the amount of cells of G₀/G₁ phase in a dose-dependent manner; B16-BL6 cells became apoptosis in the presence of Oridonin, simultaneously the amount of cells of G₂/M phase decreased while the amount of cells of G₀/G₁ phase increased in a time-dependent manner; the distribution of cell cycle of Eca109 cells changed the same way as the BGC823 cells caused by Oridonin in a time-dependent manner.Oridonin was highly effective against several kinds of tumor xenografts in vivo. In BGC823 tumor xenograft, the tumor weight in the Oridonin-treated group(75 mg·kg^-1) was 70.7% smaller than in the control group, the result of immunohistochemical staining showed Oridonin reduced the expression of MMP-2,MMP-9 of the tumor xenograft . Oridonin(40 mg·kg^-1) inhibited B16-BL6 murine melanoma xenograft, and inhibitory rate was 55.8%. It prevented the occurrence of experimental pulmonary metastasis in B16-BL6 cells, the inhibitory rate was 43.3%. In H22 tumor xenograft, the inhibitory rate of 32.6% was obtained in the Oridonin-treated group(75 mg·kg^-1) compared with the control group.By DNA microarray gene chip assay, Oridonin changed the expression of 90 genes including the 17 up-regulated genes and 73 down-regulated genes of the tested 2747 genes in associated with carcinoma of the gastric tumor BGC823 xenograft.These genes whose expression were changed by Oridonin included those participated in the cell signal transduction, apoptosis, cell cycle arrest, invision and metastasis, angiogenesis, immunity response, drug resistence of cancer.The present study indicated Oridonin was absolutely effective to variety of cancers, and its mechanism was mailly about the arrest of the cancer cell cycle, the occurrence of apoptosis of cancer cells, the suppression of the tumor invasion, metastasis, et al.