| Abstract: | cristine(VCR)的肺癌細胞株(PC-9/VCR)來探討細胞抗藥特性及克服抗藥 性M(PC-9/VCR)比較，VCR在PC-9/VCR細胞中的累積量降低。以Northern及 SouPC-9/VCR細胞無P-醣蛋白及葡萄醣運送蛋白(GLUT-1)之增生,同時 verapami P-醣蛋白之功能而降低抗藥性，故此細胞是屬於一種非P-醣 蛋白及非葡萄薑壯傶藺妦茩M。此外,PC-9/VCR細胞除了對nocodazole, cis-3,4,5,4-tetra,vinblastine及colchicine等細胞骨架之干擾劑有交 叉抗性外,對機制不同的抗癌藥如 actinomycin, adrinmycin, cisplastin, L-pam的交 抗性, 且兩種細胞對adriamycin?顯示細胞骨 架與VCR的堆積量及抗藥有關。我們發現抗藥性細胞內微管蛋比例增加,而 細胞骨架合成的抑制劑cytochalasinB,D,taxol均可改變PC-9/祪n量,進而 逆轉抗藥性。我們也發現在PC-9/VCR之細胞族群中有40%的細胞赤?菮吽C 進一步以螢光染色法及細胞分析儀測得PC-9/VCR較PC-9細胞含有actin), 以洋菜膠去除抗藥性細胞之附著性後,肌動蛋白的量隨之 藺妦茩M內累積 量也增加,顯示細胞骨架的含量、聚合的比例與VCR的累積量疑鰜Y。另外 PC-9/VCR細胞內雖含有較多量的GSH,但GSH無法降低VCR的毒性L關。有關 抗藥性的逆轉,我們發現維它命C可提高抗藥性細胞對VCR之吸收貽骨架及 DNA的破壞無關。又維它命C可降低細胞內pH值及ATP量,而增加乳酸胞使死 亡。這可能是維它命C逆轉抗藥性的一種重要機轉。 A human lung cancer PC-9 subline with acquired resistance tochemotherapeutic agent, was established with incrementale drug. The resistant PC-9 subline(PC-9/VCR) shows a 10-12 foldistance to VCR and a unique cross-resistance pattern:lowere to actinomycin D(1.8-fold),cisplatin(1.2-fold) andfold) and a sensitivity to melphalan and VP-16 which is similarntal cell line. A reduced accumulation of VCR in the resistant cells was demonstrated. DNA Southern- and RNAybridization analyses indicated that PC-9/VCR cells did noted mdr gene, overexpress P- glycoprotein and Glut-1. Theblocker verapamil and cyclosporin A, which acts as a competitiveglycoprotein, did not affect the resistant phenotype of PC-9/VCRion, PC-9/VCR showed cross- resistance to cytoskeleton inhibitorsine, nocodazole, vinblastine and cis-3,4,5,4-tetramethoxystilbene. There was no apparentDM-accumulation in PC-9/VCR cells. Compared to the PC-9 cells,ells showed enhanced vincristine cytotoxicity by cytochalasin B,Dincreased cytotoxicity was associated with the increasedd decreased efflux of vincristine by cytochalasin B and D. Thein the PC-9/VCR cells were higer than that in the PC-9 parentalion of the expression of actin in the detached adherent cells could enhance accumulation in theThese results suggested that the cellular cytoskeletones mightnt role in VCR resistance in the PC-9 human lung cancer cellresistance of PC-9/ VCR cells was partially reversed by ascorbicon, the concentration of ATP as well as the lactic acid werehe intracellular pH was dramatically decreased in the PC-9/ VCRorbic acid treatment. |
