The aim of the present study was to investigate the mechanisms underlying the radiation-sensitising effect from antennapedia proteins (ANTP)-SmacN7 on induction of apoptosis in lung cancer cells irradiated with high-LET ionizing irradiation (IR) from accelerated carbon and iron particles.
Two cultured human non-small lung cancer (NSCLC) cell lines, A549 and NCI-H460, were irradiated with low-LET X-irradiations or high-LET IR with or without treatment of ANTP-SmacN7. Change of cell survival, induction of apoptosis and cell cycle progression, and alterations in both death and survival signals for apoptosis, were studied by colony formation assay, flowcytometry, and Western blot analysis, respectively.
Showed that at the LD50 for clonogenic cell killing by high-LET iron particles, compared to the low-LET X-rays irradiations, high-LET IR was more efficient for clonogenic cell killing and induction of apoptosis, which was correlated with cell G2/M phase progression. In addition, ANTP-SmacN7 markedly promoted apoptotic cell killing through inhibition of X-linked inhibitor of apoptosis protein (XIAP) and activation of caspase-3 and 9. Furthermore, both antiapoptotic and proapoptotic molecular response was correlated with the apoptotic cell killing and in accordance with the results of clonogenic cell killing.
These findings provide useful information to contribute to the improvement of high-LET clinical radiotherapy for NSCLC from the point of view of pharmaceutical radio-sensitization.
Institute of Modern Physics, Chinese Academy of Sciences, Lanzhou, PRC.
Has not received any funding.
The author has declared no conflicts of interest.