Lin Li-Wu, Sun Yan, He Yi-Mi, Gao Shang-Da, Xue En-Sheng, Lin Xiao-Dong, Yu Li-Yun, Lin Xiu-Fang, Yang Ying-Hong
Department of Ultrasound, Union Hospital, Fujian Medical University, Fuzhou 350001, China.
Hepatobiliary Pancreat Dis Int. 2004 Feb;3(1):49-54.
Unresectable hepatocellular carcinoma (HCC) lacks effective therapy and entails very poor progress. In 1991, we found that Chinese herbal compound Star-99 has potentially effect on HCC. The purpose of this study was to probe the anti-cancer effect and the mechanism of focal injection of Chinese herbal compound Star-99 into HCC of mice.
In 32 nude mice transplanted with human hepatocellular carcinoma SMMC-7721, 16 received hypodermic implant and the other 16 orthotopic liver transplant. They were randomly divided into three groups: Star-99 group (Chinese herbal compound, 16 mice), alcohol group (8) and saline group (8), respectively. Intratumoral injection of Star-99, alcohol and saline was carried out 10 days after transplantation of HCC. Twenty days after the first injection, the nude mice were killed after being injected every 5 days with a total of 4 injections in each mouse. Tumor tissues were examined pathologically or via an electron microscope and flow cytometrical (FCM) DNA analysis. The three diameters of the tumor were measured with high-frequency ultrasound before and after injection, and the growth index was calculated with the following formula: volume of tumor (after treatment-before treatment)/volume of tumor (before treatment). Double-blind method was applied in the experiment.
The growth index of the Star-99 group (0.068+/-0.022) and the alcohol group (0.079+/-0.024) was markedly lower than that of the saline group (4.345+/-1.453, P<0.01), but there was no significant difference between the Star-99 and alcohol groups. Coagulation (8/8) was the major pathological change in the alcohol group. In the Star-99 group, however, the phenomenon of lymphocytes attacking cancer cells could even be seen under the electron microscope. The typical apoptosis cells and apoptosis bodies as well as the collagen fibrae lined in mass could also be seen in the group (14/16). FCM DNA analysis showed that the rate of apoptosis in the Star-99 group (93.8%) was significantly higher than that in the alcohol (12.5%) and saline groups (12.5%) (P<0.01).
This study shows that Star-99 markedly inhibits and destructs hepatocellular cancer cells. Star-99 is effective to directly destroy the membrane, cytoplasm and nuclei of tumor cells, causing their crumbling, activate the immune function and inflammatory reaction of nude mice, and induce the apoptosis of cancer cells. The effect of Star99 is significantly different from that of alcohol that mainly causes coagulation of cancer cells. Star-99 is feasible in the treatment of HCC.
无法切除的肝细胞癌（HCC）缺乏有效的治疗方法，病情进展极差。1991年，我们发现中药复方星-99对肝癌具有潜在作用。本研究旨在探讨中药复方星-99局部注射到小鼠肝癌组织中的抗癌作用及其机制。
将32只移植人肝细胞癌SMMC-7721的裸鼠，16只进行皮下接种，另16只进行原位肝移植。将它们随机分为三组：星-99组（中药复方，16只小鼠）、酒精组（8只）和生理盐水组（8只）。肝癌移植后10天进行瘤内注射星-99、酒精和生理盐水。首次注射后20天，每5天注射一次，每只小鼠共注射4次后处死裸鼠。对肿瘤组织进行病理检查、电子显微镜检查及流式细胞仪（FCM）DNA分析。注射前后用高频超声测量肿瘤的三个直径，并按以下公式计算生长指数：肿瘤体积（治疗后-治疗前）/肿瘤体积（治疗前）。实验采用双盲法。
星-99组（0.068±0.022）和酒精组（0.079±0.024）的生长指数明显低于生理盐水组（4.345±1.453，P<0.01），但星-99组与酒精组之间无显著差异。酒精组的主要病理变化为凝固性坏死（8/8）。而在星-99组，电镜下甚至可见淋巴细胞攻击癌细胞的现象。该组还可见典型的凋亡细胞和凋亡小体以及大量排列的胶原纤维（14/16）。FCM DNA分析显示，星-99组的凋亡率（93.8%）明显高于酒精组（12.5%）和生理盐水组（12.5%）（P<0.01）。
本研究表明星-99能显著抑制和破坏肝癌细胞。星-99可有效直接破坏肿瘤细胞的细胞膜、细胞质和细胞核，使其崩解，激活裸鼠的免疫功能和炎症反应，并诱导癌细胞凋亡。星-99的作用与主要引起癌细胞凝固性坏死的酒精有显著差异。星-99治疗肝癌是可行的。
