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部分肝切除术增强了 CC531 大鼠结直肠癌细胞在体外和体内的生长。

Partial hepatectomy enhances the growth of CC531 rat colorectal cancer cells both in vitro and in vivo.

机构信息

Department of Surgery and Radiology and Physical Medicine, Faculty of Medicine and Nursing, University of the Basque Country (UPV/EHU), Barrio Sarriena s/n, 48940, Leioa, Vizcaya, Spain.

Biocruces Bizkaia Health Research Institute, Plaza de Cruces s/n, 48903, Barakaldo, Spain.

出版信息

Sci Rep. 2021 Mar 8;11(1):5356. doi: 10.1038/s41598-021-85082-z.

Abstract

Partial hepatectomy (PHx) is the gold standard for the treatment of colorectal cancer liver metastases. However, after removing a substantial amount of hepatic tissue, growth factors are released to induce liver regeneration, which may promote the proliferation of liver micrometastases or circulating tumour cells still present in the patient. The aim of this study is to assess the effect of PHx on the growth of liver metastases induced by intrasplenic cell inoculation as well as on in vitro proliferation of the same cancer cell line. Liver tumours were induced in 18 WAG/RijHsd male rats, by seeding 250,000 syngeneic colorectal cancer cells (CC531) into the spleen. The left lateral lobe of the liver was mobilized and in half of the animals it was removed to achieve a 40% hepatectomy. Twenty-eight days after tumour induction, the animals were sacrificed and the liver was removed and sliced to assess the relative tumour surface area (RTSA%). CC531 cells were cultured in presence of foetal calf serum, non-hepatectomised (NRS) or hepatectomized rat serum (HRS), and their proliferation rate at 24, 48, and 72 h was measured. RTSA% was significantly higher in animals which had undergone PHx than in the controls (non-hepatectomised) (46.98 ± 8.76% vs. 18.73 ± 5.65%; p < 0.05). Analysing each lobe separately, this difference in favour of hepatectomized animals was relevant and statistically significant in the paramedian and caudate lobes. But in the right lobe the difference was scarce and not significant. In vitro, 2.5% HRS achieved stronger proliferative rates than the control cultures (10% FCS) or their equivalent of NRS. In this experimental model, a parallelism has been shown between the effect of PHx on the growth of colorectal cancer cells in the liver and the effect of the serum on those cells in vitro.

摘要

部分肝切除术(PHx)是治疗结直肠癌肝转移的金标准。然而,在切除大量肝组织后,生长因子被释放以诱导肝再生,这可能促进仍存在于患者体内的肝微转移或循环肿瘤细胞的增殖。本研究旨在评估 PHx 对脾内细胞接种诱导的肝转移生长的影响,以及对同一癌细胞系体外增殖的影响。通过将 250,000 个同源结直肠癌细胞(CC531)接种到脾脏中,在 18 只 WAG/RijHsd 雄性大鼠中诱导肝肿瘤。游离肝脏的左外侧叶,在一半动物中切除以实现 40%的肝切除术。肿瘤诱导后 28 天,处死动物并切除肝脏,切片评估相对肿瘤表面积(RTSA%)。将 CC531 细胞在胎牛血清(NRS)或肝切除大鼠血清(HRS)存在的情况下培养,并在 24、48 和 72 小时测量其增殖率。与非肝切除(NRS)对照相比,接受 PHx 的动物的 RTSA%明显更高(46.98±8.76%比 18.73±5.65%;p<0.05)。单独分析每个叶,这种有利于肝切除动物的差异在正中叶和尾状叶中是相关的且具有统计学意义。但在右叶,差异很小且无统计学意义。在体外,2.5% HRS 比对照培养物(10% FCS)或其等效 NRS 实现更强的增殖率。在这个实验模型中,在 PHx 对肝脏中结直肠癌细胞生长的影响和血清对这些细胞在体外的影响之间显示出了一种平行关系。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9e65/7970880/f13ab5f2e96f/41598_2021_85082_Fig1_HTML.jpg

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