Cai Hui-Hua, Sun Yue-Ming, Bai Jian-Feng, Shi Yi, Zhao Han-Lin, Miao Yi
Department of Minimally Invasive Surgery, First Affiliated Hospital, Nanjing Medical University, Nanjing 210029, China.
Hepatobiliary Pancreat Dis Int. 2008 Feb;7(1):76-81.
In recent years, recombined human growth hormone (rhGH) has been increasingly used in patients to help them recover from operation. But GH, as a mitogen, can promote cell renewal and increase malignant transformation. In the current study, we assessed the proliferation of a bile duct cancer cell line (QBC939) in vitro with GH and explored the possible relationship with the axis of GH-IGFs (insulin-like growth factors).
QBC939 cells in the exponential growth stage were harvested and divided into an experimental group (GH group) and a control group (NS group). The GH group was divided into four sub-groups according to the dose of GH and culture time (50 microg/L for 2 hours, 50 microg/L for 24 hours, 100 microg/L for 2 hours, 100 microg/L for 24 hours). The NS group was divided into two sub-groups (NS for 2 hours and NS for 24 hours). After 2 or 24 hours, IGF-1 and IGF-2 were detected using the enzyme-linked immunosorbent assay. The QBC939 cells cultured for 24 hours with two GH concentrations were made into single cell suspensions and samples underwent subsequent cell cycle evaluation. Messenger RNA of IGF-1 and IGF-2 receptor (IGF-1RmRNA and IGF-2RmRNA) were tested with the method of in situ hybridization.
There was no statistically significant difference between the GH and NS groups after 2 hours of culture (P>0.05). But after 24 hours of culture, GH stimulated cell growth in vitro and also elevated the percentage in S phase and the proliferation index (P<0.05). IGF-1RmRNA and IGF-2RmRNA were expressed in QBC939 in contrast to the blank group. The expression of IGF-1RmRNA increased with the dose of GH, but IGF-2RmRNA did not.
GH can stimulate QBC939 cell growth and proliferation in vitro and the mechanism is most likely by the GH-IGF-1-IGF-1R axis.
近年来,重组人生长激素(rhGH)在患者中越来越多地用于帮助其术后恢复。但生长激素(GH)作为一种促分裂原,可促进细胞更新并增加恶性转化。在本研究中,我们在体外评估了GH对胆管癌细胞系(QBC939)增殖的影响,并探讨了其与GH-胰岛素样生长因子(IGFs)轴的可能关系。
收集指数生长期的QBC939细胞,分为实验组(GH组)和对照组(NS组)。GH组根据GH剂量和培养时间分为四个亚组(50μg/L培养2小时、50μg/L培养24小时、100μg/L培养2小时、100μg/L培养24小时)。NS组分为两个亚组(NS培养2小时和NS培养24小时)。培养2或24小时后,采用酶联免疫吸附测定法检测IGF-1和IGF-2。将用两种GH浓度培养24小时的QBC939细胞制成单细胞悬液,随后对样本进行细胞周期评估。采用原位杂交法检测IGF-1和IGF-2受体的信使核糖核酸(IGF-1RmRNA和IGF-2RmRNA)。
培养2小时后,GH组和NS组之间无统计学显著差异(P>0.05)。但培养24小时后,GH刺激体外细胞生长,并提高了S期百分比和增殖指数(P<0.05)。与空白组相比,QBC939中表达IGF-1RmRNA和IGF-2RmRNA。IGF-1RmRNA的表达随GH剂量增加而增加,但IGF-2RmRNA的表达未增加。
GH可刺激体外QBC939细胞生长和增殖,其机制很可能是通过GH-IGF-1-IGF-1R轴。