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Resistance of colon cancer cells to long‐term 5‐fluorouracil exposure is correlated to the relative level of Bcl‐2 and Bcl‐XL in addition to Bax and p53 status
Abstract
Defects in apoptosis have been implicated in chemoresistance of colon cancer cells. We report here the ability to resist to 5‐fluorouracil‐induced apoptosis of 8 colon cancer cell lines differing in p53 and bax status: p53−/0 bax+/+ for TC7, SW480, HT‐29; p53+/+bax−/− for LS174T, LoVo; p53+/+ bax+/− for HCT116; p53+/+ or p53+/0 bax+/+ for LS513 or HCT‐EB, respectively. To approximate to the in vivo therapy, the cell lines were exposed to a long‐term treatment of 5‐FU. The analysis of proteins implicated in the apoptotic pathway has shown that the independent analysis of p53 or bax status was not sufficient to predict the extent of drug‐resistance of all cell lines. In p53+/+ cell lines but not in p53−/0 cell lines, a low level of the pro‐apoptotic Bax protein was correlated with a greater resistance of cells to 5‐FU. In addition, we found that high levels of anti‐apoptotic Bcl‐2 and Bcl‐x L proteins combined with a low level of Bax were correlated to high 5‐FU resistance of wild‐type p53 cell lines. The same correlation was obtained for 2 out of 3 mutated p53 cell lines. In conclusion, the relative levels of Bcl‐2, Bcl‐x L and Bax may altogether contribute to determine the resistance of a majority of colon tumor cells to long‐term 5‐FU treatment, whatever their p53 status. © 2002 Wiley‐Liss, Inc.
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Tumor suppressor p53 is a direct transcriptional activator of the human bax gene
Toshiyuki, M., & Reed, J. C. (1995) · Cell · doi:10.1016/0092-8674(95)90412-3 · Cited by 4,063
Disruption of p53 in human cancer cells alters the responses to therapeutic agents.
Bunz, F., Hwang, P. M., Torrance, C., Waldman, T., Zhang, Y., Dillehay, L., Williams, J., Lengauer, C., Kinzler, K. W., & Vogelstein, B. (1999) · Journal of Clinical Investigation · doi:10.1172/jci6863 · Cited by 1,044
Cited by
Erler, J. T., Cawthorne, C. J., Williams, K. J., Koritzinsky, M., Wouters, B. G., Wilson, C., Miller, C., Demonacos, C., Stratford, I. J., & Dive, C. (2004) · Molecular and Cellular Biology · doi:10.1128/mcb.24.7.2875-2889.2004 · Cited by 400
Bian, Z., Jin, L., Zhang, J., Yin, Y., Quan, C., Hu, Y., Feng, Y., Liu, H., Fei, B., Mao, Y., et al. (2016) · Scientific Reports · doi:10.1038/srep23892 · Cited by 363
MicroRNAs and colorectal cancer chemoresistance: New solution for old problem
Vaghari-Tabari, M., Majidinia, M., Moein, S., Qujeq, D., Asemi, Z., Alemi, F., Mohamadzadeh, R., Targhazeh, N., Safa, A., & Yousefi, B. (2020) · Life Sciences · doi:10.1016/j.lfs.2020.118255 · Cited by 58
Kim, K. T., Angerani, S., Chang, D., & Winssinger, N. (2019) · Journal of the American Chemical Society · doi:10.1021/jacs.9b05688 · Cited by 52
Ishiguro, M., Iida, S., Uetake, H., Morita, S., Makino, H., Kato, K., Takagi, Y., Enomoto, M., & Sugihara, K. (2007) · Annals of Surgical Oncology · doi:10.1245/s10434-006-9285-4 · Cited by 43
Metadata
- Authors
- Violette, S., Poulain, L., Dussaulx, E., Pepin, D., Faussat, A., Chambaz, J., Lacorte, J., Staedel, C., & Lesuffleur, T.
- Venue
- International Journal of Cancer
- Publisher
- Wiley
- Published
- 2002-01-22
- Volume
- 98
- Issue
- 4
- Pages
- 498-504
- ISSN
- 0020-7136 (ISSN-L)
- 1097-0215
- OpenAlex
- W2167504781
- Cited by
- 213
- References
- 2
- FWCI
- 4.54
- Type
- journal article
- Language
- en
- Open access
- closed
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- CoChat. (2026). Citation check: Resistance of colon cancer cells to long‐term 5‐fluorouracil exposure is correlated to the relative level of Bcl‐2 and Bcl‐XL in addition to Bax and p53 status. https://app.cochat.ai/papers/10.1002/ijc.10146
- The paper
- Violette, S., Poulain, L., Dussaulx, E., Pepin, D., Faussat, A., Chambaz, J., Lacorte, J., Staedel, C., & Lesuffleur, T. (2002). Resistance of colon cancer cells to long‐term 5‐fluorouracil exposure is correlated to the relative level of Bcl‐2 and Bcl‐XL in addition to Bax and p53 status. International Journal of Cancer. https://doi.org/10.1002/ijc.10146
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