热休克蛋白gp96-肽复合物体外对人肝癌细胞的抗肿瘤效应

目的研究热休克蛋白gp96-肽复合物修饰树突状细胞(DC)后对人肝癌细胞的体外特异抗肿瘤效应。方法从人原发性肝癌组织中提取gp96-肽复合物,用其修饰DC细胞后与T淋巴细胞共同培养,以MTT法检测该复合物介导的细胞毒性T细胞(CTL)对不同来源人肝癌细胞的抗肿瘤效应,并与粗提抗原修饰DC细胞组相比较。结果 gp96-肽复合物诱导的CTL对原代肝癌细胞杀伤效率为74.3%,明显高于粗提抗原组(42.5%)和未加抗原组(14.4%)(P<0.01),粗提抗原组对肝癌细胞杀伤效率高于未加抗原组(P<0.01)。且该复合物的抗肿瘤效应具有一定的组织特异性。结论 gp96-肽复合物修饰的DC细胞,在体外能刺激产生特异的抗肿瘤细胞毒性T细胞,因而热休克蛋白gp96在肿瘤免疫治疗中具有重要的实用价值。     

大鼠肝细胞癌变过程中热休克蛋白gp96的异常表达及变化特征

目的 探讨大鼠肝细胞癌变过程中热休克蛋白(HSP)gp96的表达与变化特征.方法 以2-乙酰氨基芴(2-FAA)喂饲SD大鼠诱发肝癌,以免疫组化染色及Western blot观察大鼠肝组织中Sp96蛋白的定位及表达水平.结果 SD大鼠在喂饲2-F从后,在诱癌早期肝细胞发生颗粒样变性,中期出现不典型增生,后期见大量癌巢结节.癌变过程中肝组织gp96蛋白主要定位于细胞浆,表达水平从变性组到癌前组到癌变组呈明显的梯度增加,均显著高于对照组肝组织(P＜0.01).结论 gp96参与肝细胞的癌变过程,癌变初期的过度表达有助于肝癌的早期诊断.

Abstract：

Objective To investigate the character of expression and alteration of heat shock protein (HSP) gp96 during hepatocellular carcinoma(HCC) development.Methods Rat HCC models were induced with 2.acetamidoflurene(2-FAA) in male SD rats.The location of gp96 in rat liver tissues were analyzed by immunohistochemistry and the expression levels were semi-quantitatively detected by Western blot.Results Histological examinations suggested that hepatocytes in rats fed with 2-FAA showed vacuole-like denaturations at the early stages,then dysplastic nodules appeared at the middle stage,and finally progressed to tubercles of cancerous nest.During the process,the liver gp96 protein was mostly located in cytoplasm and an increasing tendency of its levels Was found from degeneration to precancerous to cancerOUS tissues,all of them were significant higher than that in normals(P<0.01).Conclusion HSP gp96 involved in HCC development and its overexpression could be a useful marker for early diagnosis of HCC.