摘要
目的研究选择性环氧合酶2(cyclooxygenase2,COX2)抑制剂美洛昔康对肝癌生长的影响。方法采用甲基3H胸腺嘧啶核苷(3H TdR)掺入、AnnexinV荧光标记法与TdT介导的dUTP缺口末端标记(TUNEL)法检测美洛昔康对体外培养人肝癌HepG2细胞生长的影响及凋亡的诱导作用。建立裸鼠人肝癌原位移植瘤模型,给予美洛昔康治疗8周,观察其对裸鼠体内肝癌生长的影响。用免疫组化法检测美洛昔康对肝癌细胞及组织中增殖细胞核抗原表达的影响。结果美洛昔康可明显降低肝癌细胞的3H TdR掺入,其抑制作用与药物浓度呈明显正相关;美洛昔康还可诱导人肝癌细胞凋亡,其诱导的早期及晚期凋亡细胞阳性率分别为(21.7±2.4)%和(31.7±3.1)%。美洛昔康可抑制裸鼠人肝癌原位移植瘤生长,其抑瘤率为55.1%。美洛昔康还能明显抑制肝癌细胞和组织中PCNA表达。结论美洛昔康能有效抑制肝癌生长。
OBJECTIVE:To investigate the effects of selective COX-2 inhibitor meloxicam on the growth of hepatocellular carcinoma in vivo and in vitro. METHODS: The effects of meloxicam on the proliferation and the apoptosis of HepG2 cells were measured by 3H-thymidine incorporation into DNA, Annexin Ⅴ labeled assay and the TdT-mediated dUTP nick end labling in situ assay (TUNEL). HepG2 human hepatocellular carcinoma cell line was implanted orthotopically in the liver of nude mice. Meloxicam was administered for eight weeks in order to observe its influence on the growth of liver cancer. Immunohistochemistry method was used to detect the expression of proliferation cell nuclear antigen (PCNA) in liver cancer cells and tissues. RESULTS: 3H-TdR incorporation into HepG2 cells was significantly decreased through octreotide showing a concentration dependence. Meloxicam also induced the HepG2 cells apoptosis. The rates of the early and the late stage of apoptosis were (21.7±2.4)% and (31.7±3.1)%, respectively. At necropsy, meloxicam inhibited significantly the growth of orthotopical liver cancer, and the inhibition rate for tumors was 55.1 %. The expression levels of PCNA in HepG2 cells and the tissue of transplant tumors reduced apparently by meloxicam. CONCLUSION: Meloxicam is effective in inhibiting the growth of hepatocellular carcinoma in vivo and in vitro.
出处
《肿瘤防治杂志》
2005年第7期490-494,共5页
China Journal of Cancer Prevention and Treatment
基金
国家杰出青年科学基金资助项目(39725012)
关键词
癌
肝细胞
噻嗪类
环氧化合物
生长
细胞凋亡
carcinoma, hepatocellular
thiazines
epoxy compounds
growth
apoptosis
