Fang Chi-Hua, Zhang Gang-Qing, Zhu Xin-Yong, Gong Jia-Qing
Department of Hepatobiliary Surgery, Zhujiang Hospital of the First Military Medical University, Guangzhou 510282, China.
Hepatobiliary Pancreat Dis Int. 2004 Aug;3(3):433-9.
This study was designed to assess the roles of oval cells and c-myc mRNA in the process of hepatocarcinogenesis and to clarify the function of carcinogene c-myc in the development of hepatocellular carcinoma (HCC) and the mechanism of inhibitory function of uscharidin on HCC in mouse hepatocarcinogenesis.
A total of 120 clean SD mice were divided into normal group, cancer induction group, and intervention group. The normal group was fed with standard forage while the rest two groups were given p-dimethylaminoazobenzene (DAB) to induce cancer. Thirteen weeks after induction of cancer, the two groups were fed with standard forage and water. Once the pattern was set up, the intervention group was given uscharidin injection into the abdominal cavity from the first week to the 14th week. On the 2nd, 4th, 6th, 8th, 10th, 12th, 14th, 16th, 18th, 20th, 22nd, and 24th week, all mice were killed and biopsied from the liver lobe for pathological analysis. At the same time, the number of tumor nodes was counted and the expression of c-myc mRNA was tested by RT-PCR.
Since the 2nd week after cancer induction, proliferated oval cells could be seen in the portal area. Initially, the oval cells appeared in the cortical layer of the portal area, then proliferated gradually and immigrated into the liver parenchyma. In the period of fibrosis after liver proliferation, proliferated heaps of oval cells were noted in both portal and peripheral areas. In the period of carcinomatous change, oval cells could be seen both outside and inside of cancer nodes, but most of them were distributed outside. The c-myc gene was expressed negatively in the liver tissue of mice. The quantity of the expression began to increase at the time of infection of the liver and tended to increase with the degree of hepatic injury. In the period of canceration, the expression level of c-myc mRNA increased gradually. The intervention of uscharidin could not inhibit but delay the increase of the expression of c-myc mRNA.
Oval cells are closely related to hepatocarcinoma cells, which play an important role in the occurrence and development of hepatocarcinogenesis. Uscharidin can inhibit the occurrence of hepatocarcinogenesis or local spreading at the early stage of cancer induction by DAB, but it cannot inhibit the expression of c-myc.
本研究旨在评估卵圆细胞和c-myc mRNA在肝癌发生过程中的作用,阐明致癌基因c-myc在肝细胞癌(HCC)发生发展中的功能以及乌沙胆碱在小鼠肝癌发生过程中对HCC抑制作用的机制。
将120只清洁级SD小鼠分为正常组、致癌诱导组和干预组。正常组给予标准饲料,其余两组给予对二甲氨基偶氮苯(DAB)诱导致癌。致癌诱导13周后,两组均给予标准饲料和水。模型建立后,干预组从第1周开始至第14周腹腔注射乌沙胆碱。在第2、4、6、8、10、12、14、16、18、20、22和24周,处死所有小鼠,取肝叶组织进行病理分析。同时,计数肿瘤结节数量,并通过RT-PCR检测c-myc mRNA的表达。
致癌诱导后第2周起,门管区可见增殖的卵圆细胞。最初,卵圆细胞出现在门管区皮质层,随后逐渐增殖并移入肝实质。在肝脏增殖后的纤维化期,门管区和周边区均可见大量增殖的卵圆细胞堆积。在癌变期,癌结节内外均可看到卵圆细胞,但大多数分布在癌结节外。c-myc基因在小鼠肝脏组织中呈阴性表达。其表达量在肝脏感染时开始增加,并随肝损伤程度加重而呈上升趋势。在癌变期,c-myc mRNA表达水平逐渐升高。乌沙胆碱干预不能抑制但可延缓c-myc mRNA表达的升高。
卵圆细胞与肝癌细胞密切相关,在肝癌发生发展中起重要作用。乌沙胆碱可抑制DAB致癌诱导早期肝癌的发生或局部扩散,但不能抑制c-myc的表达。