Bombesin marine toxin conjugates inhibit the growth of lung cancer cells.
Bombesin marine toxin conjugates inhibit the growth of lung cancer cells.
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DOI：
10.1016/j.lfs.2008.01.019
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发表时间：
2008-04
期刊：
影响因子：
6.1
通讯作者：
T. Moody;T. Pradhan;S. Mantey;R. Jensen;M. Dyba;Deborah L. Moody;N. Tarasova;C. Michejda
中科院分区：
文献类型：
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作者：
T. Moody;T. Pradhan;S. Mantey;R. Jensen;M. Dyba;Deborah L. Moody;N. Tarasova;C. Michejda
海米斯特林（Hemiasterlin，Hem）和多拉司他丁（dolastatin，Dol）是海洋天然产物，对癌细胞具有细胞毒性。将三肽Hem和六肽Dol用接头（L）缀合至通用BB激动剂DPhe-Gln-Trp-Ala-瓦尔-βAla-His-Phe-Nle-NH 2（BA 1），并研究Hem-BB和Dol-BB缀合物对NCI-H1299肺癌细胞的作用。Hem-LA-BA 1和Hem-LB-BA 1抑制特异性（125 I-Tyr 4）BB与NCI-H1299细胞（具有BB 2受体（R））的结合，IC 50值分别为15和25 nM。将Hem-LA-BA 1和Hem-LB-BA 1添加到含有BB 2 R的Fura-2 AM负载的细胞中，引起胞浆Ca 2+升高。在生长测定中，Hem-LA-BA 1和Hem-LB-BA 1抑制NCI-H1299细胞的增殖。Dols-LD-BA 1和Dols-LE-BA 1与NCI-H1299细胞具有高亲和力结合，并升高细胞内Ca 2+，但不抑制NCI-H1299细胞的增殖。Hem-LA-BA 1还可抑制125 I-DTyr-Gln-Trp-Ala-Val-βAla-His-Phe-Nle-NH 2（BA 2）与转染BB 1 R或BB 2 R以及BRS-3的Balb/3 T3细胞的结合，IC 50值分别为130、8和540 nM。这些结果表明Hem-BB缀合物对含有BB 2 R的癌细胞具有细胞毒性。
Hemiasterlin (Hem) and dolastatin (Dol) are marine natural products which are cytotoxic for cancer cells. Hem, a tripeptide, and Dol, a hexapeptide, were conjugated with linkers (L) to the universal BB agonist DPhe-Gln-Trp-Ala-Val-βAla-His-Phe-Nle-NH2(BA1) and the effects of the Hem-BB and Dol-BB conjugates investigated on NCI-H1299 lung cancer cells. Hem-LA-BA1 and Hem-LB-BA1 inhibited specific (125I-Tyr4)BB binding to NCI-H1299 cells, which have BB2receptors (R), with IC50values of 15 and 25 nM, respectively. Addition of Hem-LA-BA1 and Hem-LB-BA1 to Fura-2 AM loaded cells containing BB2R, caused elevated cytosolic Ca2+. In a growth assay, Hem-LA-BA1 and Hem-LB-BA1 inhibited the proliferation of NCI-H1299 cells. Dol-succinamide (Dols)-LD-BA1 and Dols-LE-BA1 bound with high affinity to NCI-H1299 cells and elevated cytosolic Ca2+, but did not inhibit the proliferation of NCI-H1299 cells. Also, Hem-LA-BA1 inhibited125I-DTyr-Gln-Trp-Ala-Val-βAla-His-Phe-Nle-NH2(BA2) binding to Balb/3T3 cells transfected with BB1R or BB2R as well as with BRS-3 with IC50values of 130, 8, and 540 nM, respectively. These results show that Hem-BB conjugates are cytotoxic for cancer cells containing BB2R.