Proliferation of Colo-357 pancreatic carcinoma cells and survival of patients with pancreatic carcinoma are not altered by insulin glargine
Proliferation of Colo-357 pancreatic carcinoma cells and survival of patients with pancreatic carcinoma are not altered by insulin glargine
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DOI：
10.2337/dc07-2015
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发表时间：
2008-06-01
期刊：
影响因子：
16.2
通讯作者：
Ritzel, Robert A.
中科院分区：
文献类型：
--
作者：
Erbel, Saskia;Reers, Christina;Ritzel, Robert A.
目的-据报道，长效胰岛素类似物甘精可诱导人骨肉瘤细胞系增殖，从而可能诱导或加速肿瘤生长。细胞增殖的诱导对于糖尿病患者的胰岛素治疗和携带肿瘤细胞的潜能(例如，恶性肿瘤病史)具有特别重要的意义。研究设计与方法：以甘精胰岛素或普通人胰岛素孵育人胰腺癌细胞(COLO-357)，以0-100nmol/L孵育72h后，分析细胞增殖、细胞凋亡以及胰岛素受体、胰岛素样生长因子-I受体和胰岛素受体底物(IR)2的表达水平。结果：甘精胰岛素与普通人胰岛素在调节COLO-357细胞增殖和凋亡方面无显著差异。胰岛素受体、IGF-I受体和作为两种受体信号通路下游分子的IRS2的表达水平在所测试的任何浓度下都没有改变。在高胰岛素浓度下，甘精和普通人胰岛素对胰岛素受体的下调程度相似(P<；甘精0.0001，普通人胰岛素P=0.002)。胰腺手术后中位生存期为15个月。生存分析显示，接受甘精胰岛素治疗的患者与不接受甘精胰岛素治疗的患者以及术后无糖尿病的对照组患者的存活时间相关比例相同(P=0.4，三样本比较)。结论-常规人胰岛素和甘精胰岛素可用于治疗胰腺癌患者的糖尿病。
OBJECTIVE - It was reported that the long-acting insulin analogue glargine induces cell proliferation in a human osteosarcoma cell line and therefore might induce or accelerate tumor growth. induction of cell proliferation would be particularly relevant for insulin treatment of subjects with diabetes and the potential of bearing tumor cells (e.g., a history of a malignant disease).RESEARCH DESIGN AND METHODS - Proliferation, apoptosis, and the expression levels of insulin receptor, IGF-I receptor, and insulin receptor substrate (IRS) 2 were analyzed in human pancreatic cancer cells (Colo-357) after incubation (72 h) with insulin glargine or regular human insulin at 0-100 nmol/l. A total of 125 subjects, after partial or total pancreatectomy due to pancreatic carcinoma, were analyzed over a median follow-up period of 22 months.RESULTS - There was no significant difference between glargine and regular human insulin with respect to regulation of proliferation and apoptosis of Colo-357 cells. The expression levels of insulin receptor, IGF-I receptor, and IRS2 as a downstream molecule of both receptor signaling pathways were not altered at any concentration tested. The insulin receptor was down regulated to a similar degree by glargine and regular human insulin at high insulin concentrations (P < 0.0001 for glargine, P = 0.002 for regular human insulin). The median survival time after pancreatic surgery was 15 months. Survival analysis showed that the time-dependent proportion of patients who survived was identical in patients receiving insulin glargine versus insulin treatment without glargine and control subjects without diabetes after surgery (P = 0.4, three-sample comparison).CONCLUSIONS - Regular human insulin and insulin glargine may be used to treat diabetes in patients with pancreatic cancer.