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

TLDR: It is found that anticancer drugs could activate the mitochondrial pathway of apoptosis without involvement of upstream caspases, indicating that Bcl‐2 contributes to drug resistance in SCLC, a finding that has profound therapeutic implications.

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