| Objective:To probe the anti-cancer effect and the mechanism of the ultrasound-guided local injection in hepatocellular carcinoma (HCC) with Chinese traditional medicine "Star-99". METHODS:Twenty-eight human hepatocellular carcinoma SMMC-7721 transplanted nude mice, which were hypodermic implanted patterns, were randomly divided into three groups that were Star-99 group containing 14 patterns, ethanol group and saline group containing 7 patterns respectively. Ten days after the transplantation the medicines were injected into the tumors of all the nude mice every 5 days. After being injected 4 times the nude mice were killed. The three diameters of the tumors were measured with high frequency ultrasound before and after the therapeutics and the tumor growth indexes* (TGI) were calculated. Tumor tissues were examined by using pathological, electron microscope and flow cytometry (FCM) DNA analysis. Immunohistochemistry assay was adopted to detect the expression of Ki-67 antigen in HCC. Radioimmunoassay wasused to detect the serum levels of cytokines of interleukin-2 (IL-2) and tumor necrosis factor (TNF)-alpha. Apoptotic cells were visualized by TUNEL assay. All the experiments were carried out under the double blind. RESULTS:The TGI of Star-99 group (0.076 ±0.024)was markedly lower than that of saline group ( 4.654± 1.283)(p < 0.01). It seemed to be lower than that of ethanol group (0.082 ± 0.028), but not different significantly (P >0.05). Pathologic changes in the saline group (7/7) were not remarkable. The major pathological change in the alcohol group was coagulation (7/7). In the Star-99 group, however, we saw changes of turgescent, degeneration necrosis with a large number of lymphocytes infiltration, typical apoptosis cell and apoptosis bodies as well as the collagen fibred lined in mass. In addition, lymphocytes attacking cancer cells noted under the electron microscope were remarkable (12/14). FCM DNA analysis showed that the appearance rate of the apoptosis peak in Srar-99 group was 92.9%, markedly higher than that of the ethanol group (14.3%) and the saline group (0.0%) (P <0.01). The mean apoptotic index (AI: percentage of TUNEL signal positive cells) in Star-99 group (48.98 ±5.09%)was significantly higher than that of the ethanol group (11.95 ±2.24%) and the saline group (10.48± 3.85%) (P <0.01). The Ki-67 Labeling index in Star-99 group (17.49 ±9.43%) and ethanol group (20.51 ±11.29%) were significantly lower than that of the saline group (31.98± 12.98%)(P<0.05). Serum levels of IL-2 and TNF-a were markedly higher than that of the ethanol group and the saline group (P <0.05). Correlation (r =0.499, P <0.05) was found between AI and serum level ofTNF-a. CONCLUSION:This study shows that Star-99 can markedly inhibit and destructs the hepatocellular cancer cells. Its curative effect is as good as the ethanol. The major mechanisms of Star-99 could be the followings: (1) It can direct destruct the tumor cytoplasm, cell membrane and nucleus, resulting in the crumbling of the tumor cell; (2) It can elevate the serum levels of IL-2 and TNF-a, it can excite cellular immunity and inflammatory reaction of nude mice. (3) It can induce cancer cells apoptosis. (4) It can inhibit cancer cells proliferation . The effective mechanism of the Star-99 is different from that of the ethanol. The mechanisms of exciting the immunologic function of the organism and inducing the cell apoptosis are, especially, of significance. This study will provide a new pathway of drag administration and an experimental basis for the treatment of HCC with traditional Chinese herbal, and the study of Star-99 in the treatment of tumor is of profound significance and has good prospects.
|
PDF Full Text Request