Upregulation of bcl-2 is involved in the mediation of chemotherapy resistance in human small cell lung cancer cell lines

• Verfasst von: Sartorius, Ute [VerfasserIn]
• Verfasst von: Krammer, Peter H. [VerfasserIn]
• Titel: Upregulation of bcl-2 is involved in the mediation of chemotherapy resistance in human small cell lung cancer cell lines
• Verf.angabe: Ute A. Sartorius and Peter H. Krammer
• Jahr: 2002
• Jahr des Originals: 2001
• Umfang: 9 S.
• Teil: volume:97
• Teil: year:2002
• Teil: number:5
• Teil: pages:584-592
• Teil: extent:9
• Fussnoten: First published: 01 November 2001 ; Gesehen am 14.04.2021
• Titel Quelle: Enthalten in: International journal of cancer
• Ort Quelle: Bognor Regis : Wiley-Liss, 1966
• Jahr Quelle: 2002
• Band/Heft Quelle: 97(2002), 5, Seite 584-592
• ISSN Quelle: 1097-0215
• DOI: doi:10.1002/ijc.10096
• Datenträger: Online-Ressource
• Sprache: eng
• Sach-SW: apoptosis
• Sach-SW: bcl-2
• Sach-SW: chemotherapy
• Sach-SW: mitochondria
• Sach-SW: small cell lung cancer
• K10plus-PPN: 175486998X

Abstract

Chemotherapeutic drugs eliminate cancer cells by induction of apoptosis. Resistance to chemotherapy is partly due to a decreased apoptosis rate. Here we investigated resistance to anticancer drugs in 9 small cell lung cancer (SCLC) cell lines. Apoptosis was induced by cisplatin, doxorubicin and etoposide and was found to be independent of caspase-8 expression. Since caspase-8 is essential for signal transduction of death receptor-mediated apoptosis, all known death receptor systems are thus not required for drug-induced apoptosis in SCLC. Furthermore, we found that anticancer drugs could activate the mitochondrial pathway of apoptosis without involvement of upstream caspases. Finally, by culturing 3 sensitive cell lines in subtherapeutic concentrations of etoposide, resistant cells were generated that exhibit cross-resistance to cisplatin and doxorubicin. Drug resistance was paralleled by strong upregulation of Bcl-2, which diminished apoptosis by inhibiting the loss of the mitochondrial transmembrane potential and the release of cytochrome c. The role of bcl-2 in these processes was supported by bcl-2 transfection and antisense inhibition. These results indicate that Bcl-2 contributes to drug resistance in SCLC, a finding that has profound therapeutic implications. © 2001 Wiley-Liss, Inc.