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Experimental study on ultrasound-guided intratumoral injection of 'Star-99' in treatment of hepatocellular carcinoma of nude mice

机译:超声引导下“ Star-99”瘤内注射治疗裸鼠肝细胞癌的实验研究

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AIM: To investigate the anti-cancer effect and the immuneological mechanism of ultrasound-guided intratumoral injection of Chinese medicine "Star-99" in hepatocellular carcinoma (HCC) of nude mice. METHODS: Twenty-eight human hepatocellular carcinoma SMMC-7721 transplanted nude mice, 14 of hypodermically implanted and 14 of orthotopic liver transplanted, were randomly divided into three groups of which 14 mice with Star-99, and 7 with ethanol and saline respectively. Ten days after the transplantation the medicines were injected into the tumors of all the nude mice once every 5 days. After 4 injections the nude mice were killed. The diameters of three dimension of the tumors were measured by high frequency ultrasound before and after the treatment and the tumor growth indexes~* (TGI) were calculated. Radioimmunoassay was used to detect the serum levels of interleukin-2 (IL-2) and tumor necrosis factor (TNF)-alpha. The tumor tissues were sent for flow cytometry (FCM) DNA analysis. Apoptotic cells were visualized by TUNEL assay. All the experiments were carried out by double blind method. RESULTS: The TGI of Star-99 group (0.076+-0.024) was markedly lower than that of the saline group (4.654+-1.283) (P<0.01). It also seemed to be lower than that of the ethanol group (0.082+-0.028), but not significantly different (P>0.05). Serum levels of IL-2 and TIMF-α were markedly higher than those of ethanol group and saline groups (P<0.05). 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). 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). Correlation (r=0.499, P<0.05) was found between AI and serum level of TNF-α. CONCLUSION: Star-99 has an effect on the elevation of the serum levels of IL-2 and TNF-α. It indicates that Star-99 has the function of enhancing the cellular immunity and inducing cancer cell apoptosis. The correlation between AI and serum level of TNF-α indicates that the elevation of the serum of TNF-α induced by Star-99 may be an important factor in the promotion of the hepatic cancer cell apoptosis. Star-99 has strong effects on the inhibition and destruction of cancer cells. Its curative effect is as good as ethanol. Its major mechanisms can be as follows: (1) it increases the serum levels of IL-2 and TNF-α and triggers cellular immunity. (2) It can induce cancer cells apoptosis, the effective mechanism of the Star-99 is different from that of the ethanol. The mechanisms of triggering the immunologic function of the organism and inducing cell apoptosis are, of particular significance. This study will provide a new pathway of drug administration and an experimental basis for the treatment of HCC with Chinese herbal, and the study of Star-99 in the treatment of tumor is of profound significance with good prospects.
机译:目的:探讨超声引导肿瘤内注射Star-99对裸鼠肝细胞癌(HCC)的抗癌作用及免疫机制。方法:将28只人肝癌SMMC-7721移植裸鼠,皮下植入的14只和原位肝移植的14只随机分为三组,其中Star-99小鼠14只,乙醇和生理盐水7只。移植后10天,每5天将药物注入所有裸鼠的肿瘤中。 4次注射后,将裸鼠杀死。在治疗前后,通过高频超声测量肿瘤的三个维度的直径,并计算出肿瘤的生长指数〜(TGI)。放射免疫法用于检测白细胞介素2(IL-2)和肿瘤坏死因子(TNF)-α的血清水平。将肿瘤组织送去进行流式细胞术(FCM)DNA分析。通过TUNEL测定法观察凋亡细胞。所有实验均采用双盲法进行。结果:Star-99组的TGI(0.076 + -0.024)显着低于生理盐水组(4.654 + -1.283)(P <0.01)。似乎也低于乙醇组(0.082 + -0.028),但无显着差异(P> 0.05)。血清IL-2和TIMF-α水平明显高于乙醇组和生理盐水组(P <0.05)。 Star-99组(48.98 + -5.09%)的平均凋亡指数(AI:TUNEL信号阳性细胞百分比)显着高于乙醇组(11.95 + -2.24%)和生理盐水组(10.48 +- 3.85%)(P <0.01)。 FCM DNA分析表明,Srar-99组细胞凋亡峰的出现率为92.9%,明显高于乙醇组(14.3%)和生理盐水组(0.0%)(P <0.01)。 AI与血清TNF-α水平相关(r = 0.499,P <0.05)。结论:Star-99对血清IL-2和TNF-α水平升高有影响。这表明Star-99具有增强细胞免疫力和诱导癌细胞凋亡的功能。 AI与血清TNF-α水平的相关性表明Star-99诱导的TNF-α血清升高可能是促进肝癌细胞凋亡的重要因素。 Star-99对癌细胞的抑制和破坏具有强大的作用。它的治疗效果与乙醇一样好。其主要机制可能如下:(1)它增加血清IL-2和TNF-α的水平并触发细胞免疫。 (2)它可以诱导癌细胞凋亡,Star-99的有效机制不同于乙醇。触发生物体的免疫功能和诱导细胞凋亡的机制具有特别重要的意义。该研究将为中药治疗肝癌提供新的给药途径和实验依据,而Star-99在肿瘤治疗中的研究具有重要的意义和广阔的前景。

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