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Defects in apoptotic signal transduction in cisplatin-resistant non-small cell lung cancer cells.
Oncol Rep. 2005 Jun; 13(6):1229-34.OR

Abstract

Non-small cell lung cancer (NSCLC) often shows intrinsic multidrug resistance, which is one of the most serious problems in cisplatin-based adjuvant chemotherapy. Anticancer drugs exert at least part of their cytotoxic effect by triggering apoptosis. In order to understand the molecular alterations leading to heterogeneous cisplatin sensitivity and apoptosis inducibility in NSCLC cells, we analyzed various apoptotic pathways, including the activation of caspase-8, -9 and -3, the release of cytochrome c from mitochondria and the expression levels of pro- and anti-apoptotic proteins such as Bax, Bad, Bcl-2, Bcl-xL, Fas and p53 using heterogeneously apoptosis-sensitive cells (Ma-10, Ma-31 and Ma-46). Cisplatin treatment induced the activation of caspase-8, -9 and -3 and the release of cytochrome c in apoptosis-sensitive Ma-46. The expression of Bcl-xL was the highest and p53 was not expressed in apoptosis-resistant Ma-31, and Fas was not expressed in Ma-46. These expression levels were not correlated with the apoptosis inducibility of the three cell lines. These results suggest that blockage of the apoptotic signal from mitochondria is responsible for apoptosis resistance in NSCLC cell lines. Our findings also indicate that anti-apoptotic Bcl-xL and pro-apoptotic p53 are necessary but not sufficient for resistance to cisplatin-induced apoptosis in NSCLC cells.

Authors+Show Affiliations

Graduate School of Pharmaceutical Sciences, The University of Tokushima, 1-78 Sho-machi, Tokushima 770-8505, Japan.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

15870947

Citation

Ikuta, Kenji, et al. "Defects in Apoptotic Signal Transduction in Cisplatin-resistant Non-small Cell Lung Cancer Cells." Oncology Reports, vol. 13, no. 6, 2005, pp. 1229-34.
Ikuta K, Takemura K, Kihara M, et al. Defects in apoptotic signal transduction in cisplatin-resistant non-small cell lung cancer cells. Oncol Rep. 2005;13(6):1229-34.
Ikuta, K., Takemura, K., Kihara, M., Naito, S., Lee, E., Shimizu, E., & Yamauchi, A. (2005). Defects in apoptotic signal transduction in cisplatin-resistant non-small cell lung cancer cells. Oncology Reports, 13(6), 1229-34.
Ikuta K, et al. Defects in Apoptotic Signal Transduction in Cisplatin-resistant Non-small Cell Lung Cancer Cells. Oncol Rep. 2005;13(6):1229-34. PubMed PMID: 15870947.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Defects in apoptotic signal transduction in cisplatin-resistant non-small cell lung cancer cells. AU - Ikuta,Kenji, AU - Takemura,Kazu, AU - Kihara,Masaru, AU - Naito,Shinsaku, AU - Lee,Eibal, AU - Shimizu,Eiji, AU - Yamauchi,Aiko, PY - 2005/5/5/pubmed PY - 2005/9/20/medline PY - 2005/5/5/entrez SP - 1229 EP - 34 JF - Oncology reports JO - Oncol Rep VL - 13 IS - 6 N2 - Non-small cell lung cancer (NSCLC) often shows intrinsic multidrug resistance, which is one of the most serious problems in cisplatin-based adjuvant chemotherapy. Anticancer drugs exert at least part of their cytotoxic effect by triggering apoptosis. In order to understand the molecular alterations leading to heterogeneous cisplatin sensitivity and apoptosis inducibility in NSCLC cells, we analyzed various apoptotic pathways, including the activation of caspase-8, -9 and -3, the release of cytochrome c from mitochondria and the expression levels of pro- and anti-apoptotic proteins such as Bax, Bad, Bcl-2, Bcl-xL, Fas and p53 using heterogeneously apoptosis-sensitive cells (Ma-10, Ma-31 and Ma-46). Cisplatin treatment induced the activation of caspase-8, -9 and -3 and the release of cytochrome c in apoptosis-sensitive Ma-46. The expression of Bcl-xL was the highest and p53 was not expressed in apoptosis-resistant Ma-31, and Fas was not expressed in Ma-46. These expression levels were not correlated with the apoptosis inducibility of the three cell lines. These results suggest that blockage of the apoptotic signal from mitochondria is responsible for apoptosis resistance in NSCLC cell lines. Our findings also indicate that anti-apoptotic Bcl-xL and pro-apoptotic p53 are necessary but not sufficient for resistance to cisplatin-induced apoptosis in NSCLC cells. SN - 1021-335X UR - https://www.unboundmedicine.com/medline/citation/15870947/Defects_in_apoptotic_signal_transduction_in_cisplatin_resistant_non_small_cell_lung_cancer_cells_ L2 - http://www.spandidos-publications.com/or/13/6/1229 DB - PRIME DP - Unbound Medicine ER -