生长激素受体在胰腺癌-慢性胰腺炎导管细胞的表达及生长激素对移植瘤PCNA的影响

Expression of growth hormone receptor in duct cells of pancreatic carcinoma-chronic pancreatitis and impact of growth hormone on PCNA of inoculated pancreatic tumor

目的观察生长激素受体(GHR)在胰腺癌-慢性胰腺炎导管细胞的表达及生长激素(GH)对移植瘤增殖细胞核抗原(PCNA)的影响。方法免疫组化法检测GHR在胰腺癌细胞(Cap- 1、Panc-1、Mia、Colo、SW-1990、Aspc、P3)、移植瘤及人胰腺癌切除标本的表达,并以人混合淋巴细胞、人正常胰腺及慢性胰腺炎导管细胞作对照;裸鼠成瘤后随机分为注射GH的实验组(GH组,按剂量及时间分为4 mg 2周、2 mg 2周、2 mg 3周3个亚组)及对照组(NS组),于最后一次注药后切除肿瘤,用免疫组化法观察GH对肿瘤细胞中PCNA表达的影响。结果GHR在各胰腺癌细胞株上有不同程度的表达;在人胰腺癌及慢性胰腺炎切除标本,GHR在导管细胞虽呈阳性表达,但与人正常胰腺的强表达形成对照,阳性率低于后者(P<0.05);胰腺癌细胞PCNA阳性率在组间无差别。结论GHR在胰腺癌、慢性胰腺炎导管细胞有一定程度的表达,但表达强度弱于正常胰腺,GH不改变肿瘤细胞中PCNA的表达。

Objective To observe the expression of growth hormone receptor （GHR） in duct cells of pancreatic carcinoma-chronic pancreatitis, and the impact of growth hormone on PCNA of inoculated pancreatic tumor. Methods A novel monoclonal antibody Mab263, directed against the hormone binding side of the receptor, was applied to immunohistochemically determine GHR expression in Cap-l, Panc-l, Mia, Colo, SW-1990, Aspc and P3 pancreatic cancer lines, inoculation tumor and clinical resection specimens （including normal pancreas, chronic pancreatitis and pancreatic cancer）. Athymic nude Balb/c mice were inoculated with SW-1990 cells. When tumors became palpable after inoculation, animals were randomized into different groups to receive GH （Group A, 4mg/kg. s. c. once daily for 2 weeks; Group B, 2mg/kg. s.c. for 2 weeks; Group C, 2mg/kg. s. c. for 3 weeks） versus saline control. At the time the animals were killed, tumor tissues were rapidly incised for subsequent pathological observation using immunohistochemical techniques. Results GHR was weakly expressed in duct cells of pancreatic carcinoma and chronic pancreatitis in contrast to other cells （including lymphocytes and normal duct cells）. GH did not change expression of PCNA in pancreatic tumor cells in vivo. Conclusion A small quantity of growth hormone receptors is detected on human pancreatic cancer cells. GH does not stimulate proliferation of pancreatic cancer cells in vivo.