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Vorinostat increases carboplatin and paclitaxel activity in non-small cell lung cancer cells
International Journal of Cancer, 09/08/09
Owonikoko TK et al. – Vorinostat interacts favorably with carboplatin and paclitaxel in NSCLC cells. This involves a vorinostat-mediated irreversible increase in DNA damage in the case of carboplatin and a reversible increase in microtubule stability in the case of paclitaxel.
Methods- Using the MTT assay 72 h after continuous drug exposure, growth inhibition of 4 NSCLC cell lines was assessed
- Vorinostat (1 microM) inhibited growth by 17%-41% in NSCLC
- Vorinostat addition to carboplatin or paclitaxel led to significantly greater growth inhibition than chemotherapy alone in all 4 cell lines
- When colony formation was measured after drug withdrawal, vorinostat significatly increased the effects of carboplatin, but not paclitaxel
- The % colony formation was control 100%; 1 M vorinostat, 83% ± 10%; 5 M carboplatin, 41% ± 11%; carboplatin/vorinostat, 8% ± 4%; 2 nM paclitaxel, 53% ± 11%; paclitaxel/vorinostat, 46% ± 21%. In A549 and 128-88T, vorinostat potentiated carboplatin induction of gamma-H2AX (aDNA damage marker) and increased -tubulin acetylation (a marker for stabilized mictrotubules)
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