Apoptosis induction therapy for pancreatic cancer cells by isoprenoids

香叶醇(GGO)和法尼醇(FO)是维生素K2的侧链，是合成的异戊二烯类化合物，它们对血细胞有生长抑制作用。我们研究了GGO和FO对胰腺癌患者腹水性癌细胞系(PANC-1、MIAPaCa-2、ASPC-I、BxPC-3、1B2C6、KP4)和新鲜胰腺癌细胞增殖的影响。GGO和FO分别在IC5020-70μM和20-60μM抑制所有癌细胞的增殖。GGO和FO刺激处理细胞DNA片段化。因此，我们对GGO和FO诱导的细胞凋亡的信号传导进行了研究。GGO和FO与P53不相关，因为所有细胞系都存在P53基因的缺失或突变。我们用ICE和CPP32抑制剂研究了caspse家族(ICE和CPP32)是否参与GGO或FO的作用。GGO和FO的作用不受两种抑制剂的影响。将胰腺癌细胞接种于裸鼠体内，观察GGO和FO对肿瘤的抑制作用，且无明显毒副作用。

Geranylgeraniol (GGO) and farnesol (FO), synthetic isoprenoids, which are the side chain of vitamine K2, have been noted for their growth inhibitory-effect on hematological cells. However, the precise mechanisms of their functions are still unclear.We investigated the effect of GGO and FO on the proliferation of sex pancreatic cancer cell lines (Panc-1, MIAPaCa-2, AsPC-I, BxPC-3, 1B2C6, KP4) and fresh cancer cells, which were isolated from ascitis of three pancreatic cancer patients. GGO inhibited the proliferation of all these cancer cells at 20-70μM of IC50 and FO did at 20-60μM of IC50. GGO and FO stimulated DNA fragmentation of treated cells. Therefore, we studied on the signal transudation of apoptosis induced by GGO and FO. P53 is not to be implicated to apoptosis by GGO and FO, because all cell lines have deletion or mutation on p53 gene. We studied whether caspse family (ICE and CPP32) was involved in the effect of GGO or FO by using ICE and CPP32 inhibitors. Effect of GGO and FO were not affected by both inhibitors. Pancreatic cancer cells were inoculated in nude mise to study the effect of GGO and FO diminished the cancer tumors without obvious side effects.