Targeted cytotoxic somatostatin analog AN-162 inhibits growth of human colon carcinomas and increases sensitivity of doxorubicin resistant murine leukemia cells
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- 作者：Florian Hohla ; Stefan Buchholz ; Andrew V. Schally ; Awtar Krishan ; Ferenc G. Rick ; Luca Szalontay ; Andrea Papadia ; Gabor Halmos ; Frank Koster ; Elmar Aigner ; Christian Datz ; Stephan Seitz
- 关键词：AN-162 ; Targeted therapy ; Colon cancer ; Somatostatin ; Doxorubicin
- 刊名：Cancer Letters
- 出版年：2010
- 出版时间：1 August 2010
- 年：2010
- 卷：294
- 期：1
- 页码：35-42
- 全文大小：554 K
文摘
The effect of the targeted cytotoxic somatostatin (SST) analog AN-162, consisting of doxorubicin (DOX) conjugated to SST carrier RC-121, was investigated on the growth of human colorectal cancer (CRC) cell lines HT-29, HCT-15, and HCT-116 and a DOX-resistant mouse leukemia cell line P388/R84. mRNA for SST-receptors and high affinity binding sites for SST were detected in all CRC cell lines and in P388/R84 cells. In contrast to DOX alone, AN-162 blocked HCT-116 cells and P388/R84 cells in S/G2 phase and increased the number of apoptotic cells. In vivo, AN-162 reduced the volume of CRC xenografts more effectively than its unconjugated components. Our results suggest that AN-162 inhibits growth of experimental CRC more effectively than DOX and increases sensitivity of DOX resistant human leukemia cells.