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目的探讨ｄ－艹宁烯在化学诱发实验性肿瘤及人实体瘤的防治作用及其机制。方法采用Ｗｅｓｔｅｒｎｂｌｏｔｔｉｎｇ方法观察了ｄ－艹宁烯对胰腺癌细胞中与膜结合的ｐ２１ｒａｓ蛋白表达和法尼基蛋白转移酶活性的抑制作用。同时，采用免疫组化法观察了ｄ－艹宁烯对ｐ２１ｒａｓ在细胞膜上定位的影响。并以Ｎｏｒｔｈｅｒｎｂｌｏｔｉｎｇ方法检测ｄ－艹宁烯对Ｈ－ｒａｓ癌基因在人胰腺癌细胞系中的表达。结果ｄ－艹宁烯对人胰腺癌细胞呈现的抑制作用，其机制可能与其抑制法尼基蛋白转移酶活性，从而降低ｐ２１Ｈ－ｒａｓ蛋白的异戊二烯化修饰有关。ｄ－艹宁烯可降低ｐ２１ｒａｓ蛋白的膜结合，增加胞浆ｐ２１ｒａｓ蛋白的积蓄。在经ｄ－艹宁烯处理过的胰腺癌细胞加入抗ｐ２１ｒａｓ抗体，采用免疫组化法也可观察到上述现象。结论法尼基蛋白转移酶的抑制和ｐ２１ｒａｓ蛋白膜结合与ｐ２１ｒａｓ定位的改变密切相关。ｐ２１ｒａｓ法尼基化的抑制作用改变了它在细胞内的定位，从而影响其生物学活性，但尚未发现与Ｈ－ｒａｓ癌基因表达的密切相关。
Objective To investigate the preventive and therapeutic effects of d-fenningene on chemically induced experimental tumors and human solid tumors. Methods Western blotting method was used to observe the inhibition of membrane-bound p21ras protein expression and farnesyl protein transferase activity in pancreatic cancer cells. At the same time, the effect of d-Pyrene on the localization of p21ras on the cell membrane was observed by immunohistochemistry. Northern blotting was used to detect the expression of H-ras oncogene in human pancreatic cancer cell lines. Results The inhibitory effect of d-limonene on human pancreatic cancer cells may be related to its inhibition of farnesyl protein transferase activity, thereby reducing the prenylation of p21H-ras protein. D-quinone can reduce the membrane binding of p21ras protein and increase the accumulation of cytoplasmic p21ras protein. Anti-p21ras antibody was added to d-Pyrene-treated pancreatic cancer cells, and the above phenomenon was also observed by immunohistochemistry. Conclusion The inhibition of farnesyl protein transferase and the binding of p21ras protein are closely related to the changes of p21ras localization. Inhibition of p21ras farnesylation alters its localization in the cell and thus affects its biological activity, but no close correlation with H-ras oncogene expression has been found.