Sjöholm A, Bucht E, Theodorsson E, Larsson R, Nygren P
Department of Molecular Medicine (L6:02), Karolinska Institute, Karolinska Hospital, Stockholm, Sweden.
Mol Cell Endocrinol. 1994 Jul;103(1-2):89-94. doi: 10.1016/0303-7207(94)90073-6.
The significance of polyamines for the neoplastic proliferation and secretion of calcitonin (CT) and calcitonin-gene-related peptide (CGRP) by the human medullary thyroid carcinoma TT cell line was investigated. TT cells were cultured in vitro for 6 days with or without additions of pathway inhibitors of polyamine biosynthetic enzymes. Treatment of the cells with 1 mM of the specific L-ornithine decarboxylase (ODC) inhibitor DL-alpha-difluoromethylornithine (DFMO) resulted in a 97% decrease in ODC activity, lowered contents of putrescine (96%) and spermidine (85%) and cell proliferation rates (90%) along with a compensatory 15-fold increase in S-adenosyl-L-methionine decarboxylase (SAMDC) activity. DFMO treatment also led to a decrease in cellular content of CT (33%) and CGRP (26%), while the drug enhanced secretion of CT (31%) but depressed that of CGRP (26%), and elevated the ratio of CT to CGRP secreted into the medium by 74%. Ethylglyoxal bis(guanylhydrazone) (EGBG), a SAMDC inhibitor, at 100 microM evoked a similar reduction of cell proliferation and lowered the content of spermine by 81%. Furthermore, EGBG treatment caused a 34-fold increase in ODC activity and a subsequent 35-fold build-up of putrescine, but also seemed to stabilize SAMDC as evidenced by a highly enhanced SAMDC activity (approximately 200-fold) during enzyme assays in the absence of the inhibitor. EGBG exposure resulted in an increase in cellular CT content (110%) and secretion of the hormone (82%), while not affecting CGRP content or release.2+ EGBG effects were partially counteracted by DFMO.(ABSTRACT TRUNCATED AT 250 WORDS)
研究了多胺对人甲状腺髓样癌TT细胞系肿瘤增殖以及降钙素（CT）和降钙素基因相关肽（CGRP）分泌的意义。TT细胞在体外培养6天，添加或不添加多胺生物合成酶的途径抑制剂。用1 mM特异性L-鸟氨酸脱羧酶（ODC）抑制剂DL-α-二氟甲基鸟氨酸（DFMO）处理细胞，导致ODC活性降低97%，腐胺（96%）和亚精胺（85%）含量降低，细胞增殖率降低（90%），同时S-腺苷-L-甲硫氨酸脱羧酶（SAMDC）活性代偿性增加15倍。DFMO处理还导致CT细胞含量降低（33%）和CGRP降低（26%），而该药物增强了CT的分泌（31%）但抑制了CGRP的分泌（26%），并使分泌到培养基中的CT与CGRP的比例提高了74%。100 microM的SAMDC抑制剂双（胍腙）乙二醛（EGBG）引起类似的细胞增殖减少，并使精胺含量降低81%。此外，EGBG处理导致ODC活性增加34倍，随后腐胺积累35倍，但似乎也稳定了SAMDC，这在无抑制剂的酶测定过程中SAMDC活性高度增强（约200倍）得到证明。EGBG暴露导致细胞CT含量增加（110%）和该激素的分泌增加（82%），而不影响CGRP的含量或释放。DFMO部分抵消了EGBG的作用。（摘要截短于250字）
