Reversal of Chemoresistance in Human Lung Cancer Cell Line A549/ XXXX by Synthetic Second Mitochondria-Derived Activator of Caspase Peptide.

@entity17205 @entity5 @entity4404 @entity2 @entity1311 @entity98
BACKGROUND: Chemoresistance is a leading cause of treatment failure in advanced @entity2 , including that with the extensively prescribed @entity1311 . Recently, a series of structurally unique @entity17205 ( @entity17205 ) that act as antagonists of inhibitor of apoptosis proteins (IAPs) have been discovered, exhibiting the ability of inducing enhanced apoptosis of various @entity5 cell types when combined with chemotherapy. In the present study, we synthesized the second mitochondria-derived activator of caspase peptide ( @entity17205 -N7 for short) and explored its capacity in combination with @entity1311 in vitro. METHODS: The sensitivity assay and reversal ability of @entity17205 -N7 were tested by @entity98 . Flow cytometry was used to analyze apoptosis of cells with @entity4404 /PI double staining technique. Cell cloning ability was performed to reflect its biological behavior in each group. RESULTS: Concentrations with inhibitory rates < 10% were selected as the reversal value of @entity17205 -N7 peptide using @entity98 . The reversal folds were 2.52, 3.26, 3.67, and 5.4 in @entity1311 + @entity17205 -N7 (0.0390625, 0.078125, 0.15625, 0.3125  g/mL, respectively), and concentrations of @entity17205 -N7 and reversal folds appeared in an obvious positive correlation (r(s) = 1, p = 0.000). Apoptosis analyzed at 48 hours by flow cytometry showed the apoptotic rates in @entity1311 and 0.0390625, 0.078125, 0.15625, and 0.3125  g/mL @entity17205 -N7 + @entity1311 groups were 15.4    1.09%, 20.8%    2.18%, 28.4%    4.17%, 37.64%    6.41%, and 46.6%    7.76%, respectively. Concentrations of @entity17205 -N7 appeared to have negative correlations with PE and SF (r(s) = -1, p < 0.05), which showed that the cells' cloning ability in 0.3125  g/mL @entity17205 -N7 + @entity1311 group was worse than that of other groups. CONCLUSIONS: When combined with @entity1311 , 0.3125  g/mL @entity17205 -N7 peptide may significantly increase @entity1311 -induced apoptosis in chemoresistant A549/ @entity1311 lung cells at 48 hours, and is potentially useful as a reversal agent in @entity2 therapy.
