The IC50 value of cisplatin was significantly correlated with the ratio of Bcl-2/Bim mRNA expression in 33 SCLC cell lines (P= 0.041) as well as the ratio of Bcl-2/Bim protein expression in 7 SCLC cell lines (P= 0.0252).
Venetoclax induced BIM-dependent apoptosis <i>in vitro</i> and blocked tumor growth and induced tumor regressions in mice bearing high BCL-2-expressing SCLC tumors <i>in vivo</i> BCL-2 expression was a predictive biomarker for sensitivity in SCLC cell lines and was highly expressed in a subset of SCLC cell lines and tumors, suggesting that a substantial fraction of patients with SCLC could benefit from venetoclax.
We found that over-expression of wtGR via retroviral transduction causes the DMS 79 SCLC cell line to undergo caspase-mediated apoptosis within 72 h. Neither BAD nor BCL2L11 (BIM) mRNA and protein levels were affected by GR restoration implying that GR does not trigger apoptosis in the SCLC cell lines by up-regulating these pro-apoptotic genes.
BIM 26182 and BIM 26189 injected at the doses of 50 micrograms twice a day (s.c.) around the tumor for 10 to 21 days delayed the growth of SCLC 41 and of SCLC 75.