Long-term cultivation of colorectal carcinoma cells with anti-cancer drugs induces drug resistance and telomere elongation: an in vitro study.

作者: Noritsugu Kuranaga , Nariyoshi Shinomiya , Hidetaka Mochizuki

DOI: 10.1186/1471-2407-1-10

关键词:

摘要: The role of telomerase activation in the expression and/or maintenance drug resistance is not clearly understood. Therefore, we investigated relationships, among activity, telomere length and multidrug genes colorectal cancer cell lines cultivated with anti-cancer drugs. LoVo DLD-1 cells were continuously grown presence both CDDP 5-FU for up to 100 days. Cell proliferation, serially monitored as PDL increased. tended increase However, an abnormal aneuploid clone was detected far by a DNA histogram analysis. Tumor showing drugs revealed higher proliferation rate. gradually increased progressive PDL. activity reached maximum level at 15 27 cells. An mRNA components, especially hTERT hTR, observed same PDLs. These results suggest that high elongation telomeres appear help maintain Cancer long proliferative may thus be able better survive exposure This presumably due chromosome stability strong mdr-1 MRP genes.

参考文章(27)
A. Tsubura, H. Senzaki, D. Yamamoto, Y. Uemura, Y. Kiyozuka, S. Adachi, Jihong Yang, Correlation of chemosensitivity to anticancer drugs and telomere length, telomerase activity and telomerase RNA expression in human ovarian cancer cells. Anticancer Research. ,vol. 20, pp. 203- 212 ,(2000)
William C. Hahn, Sheila A. Stewart, Mary W. Brooks, Shoshana G. York, Elinor Eaton, Akiko Kurachi, Roderick L. Beijersbergen, Joan H.M. Knoll, Matthew Meyerson, Robert A. Weinberg, Inhibition of telomerase limits the growth of human cancer cells Nature Medicine. ,vol. 5, pp. 1164- 1170 ,(1999) , 10.1038/13495
B Forseth, D D Von Hoff, G Wahl, K Davidson, T Waddelow, J Scott, Hydroxyurea accelerates loss of extrachromosomally amplified genes from tumor cells Cancer Research. ,vol. 51, pp. 6273- 6279 ,(1991)
C.M. Counter, A.A. Avilion, C.E. LeFeuvre, N.G. Stewart, C.W. Greider, C.B. Harley, S. Bacchetti, Telomere shortening associated with chromosome instability is arrested in immortal cells which express telomerase activity. The EMBO Journal. ,vol. 11, pp. 1921- 1929 ,(1992) , 10.1002/J.1460-2075.1992.TB05245.X
C Aghajanian, D R Spriggs, G K Schwartz, X J Yan, A Husain, N Rosales, UCN-01 in ovary cancer cells: effective as a single agent and in combination with cis-diamminedichloroplatinum(II)independent of p53 status. Clinical Cancer Research. ,vol. 3, pp. 2089- 2097 ,(1997)
Yasushi Okusa, Nariyoshi Shinomiya, Takashi Ichikura, Hidetaka Mochizuki, Correlation between telomerase activity and DNA ploidy in gastric cancer. Oncology. ,vol. 55, pp. 258- 264 ,(1998) , 10.1159/000011860
Yoshiyuki Abe, Masato Nakamura, Eiichiro Ota, Yuichi Ozeki, Seiichi Tamai, Hiroshi Inoue, Yoshito Ueyama, Toshiro Ogata, Norikazu Tamaoki, Expression of the Multidrug Resistance Gene (MDR1) in Non-small Cell Lung Cancer Japanese Journal of Cancer Research. ,vol. 85, pp. 536- 541 ,(1994) , 10.1111/J.1349-7006.1994.TB02392.X
Elisabeth W. H. M. Eijdems, Marcel de Haas, José M. Coco-Martin, Cecile P. E. Ottenheim, Guido J. R. Zaman, Hans G. Dauwerse, Martijn H. Breuning, Peter R. Twentyman, Piet Borst, Frank Baas, Mechanisms of MRP over-expression in four human lung-cancer cell lines and analysis of the MRP amplicon International Journal of Cancer. ,vol. 60, pp. 676- 684 ,(1995) , 10.1002/IJC.2910600518
Fuyuki Ishikawa, Telomere crisis, the driving force in cancer cell evolution. Biochemical and Biophysical Research Communications. ,vol. 230, pp. 1- 6 ,(1997) , 10.1006/BBRC.1996.5928