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目的用小动物生物发光成像技术(简称活体成像技术)对纳米活性炭(activated carbon nanoparticles,ACNP)吸附丝裂霉素C(mitomycin C,MMC)所组成的新型淋巴靶向制剂卡波霉素(carbomycin,CBMC)的体内抗胃癌作用进行初步评价。方法将包含有荧光素酶基因的pCIBAP-Luc载体转染人胃癌BGC-823细胞系,经G418抗性筛选获得稳定高表达荧光素酶的单克隆细胞;将持续表达荧光素酶的肿瘤细胞对6组裸鼠进行腹腔种植;1周后裸鼠腹腔形成肿瘤灶,将6组动物分别腹腔给予生理盐水、ACNP、MMC、CBMC低剂量、CBMC中剂量和CBMC高剂量药物。分别于给药后7,14,21 d用IVIS活体成像系统动态监测肿瘤生长情况。结果体外影像结果显示,表达荧光素酶的细胞数量与其发光强度呈正相关;裸鼠活体成像结果显示,成功建立了高表达荧光素酶的腹腔胃癌移植模型;MMC组和3个剂量的CBMC组均较生理盐水组显著抑制肿瘤的生长;单独使用ACNP没有抗肿瘤作用;在含相同MMC药量的情况下,与MMC组相比,CBMC组能够显著抑制肿瘤的生长。结论活体成像技术可动态监测胃癌腹腔肿瘤灶的生长发展过程,是评价抗肿瘤药物CBMC的一种新的有效手段;CBMC裸鼠腹腔化疗能有效抑制胃癌细胞的生长,具有良好的临床应用前景。
OBJECTIVE: To observe the effect of adsorption of carbomycin (carbomycin), a novel lymphatic targeted preparation consisting of mitomycin C (MMC) on activated carbon nanoparticles (ACNP), using the bioluminescence imaging technology of small animals , CBMC) in vivo anti-gastric cancer preliminary evaluation. Methods pCIBAP-Luc vector containing luciferase gene was transfected into human gastric cancer cell line BGC-823, and monoclonal cells stably expressing luciferase were obtained by G418 resistance screening. The luciferase- Six groups of nude mice were peritoneally implanted. One week later, the nude mice formed tumors in the peritoneal cavity. Six animals were intraperitoneally injected with normal saline, ACNP, MMC, low dose of CBMC, middle dose of CBMC and high dose of CBMC respectively. The growth of tumor was dynamically monitored by IVIS live imaging system at 7, 14 and 21 d after administration respectively. Results The results of in vitro imaging showed that the number of luciferase-expressing cells was positively correlated with the luminescence intensity. The biopsy results of nude mice showed that the transplanted gastric cancer model with high luciferase expression was established successfully. The MMC group and the three doses of CBMC group Compared with the saline group, the growth of the tumor was significantly inhibited. ACNP alone had no antitumor effect. Compared with the MMC group, the CBMC group could significantly inhibit the growth of the tumor in the same dose of MMC. Conclusion In vivo imaging technique can dynamically monitor the growth and development of gastric cancer peritoneal neoplasms and is a new and effective method to evaluate anti-cancer drug CBMC. The intraperitoneal chemotherapy of CBMC in nude mice can effectively inhibit the growth of gastric cancer cells and has good clinical application prospects.