The combination of cisplatin and 5-fluorouracil synergistically enhances apoptosis in Hep-2 laryngeal carcinoma cells, potentially mediated by increased Smac/DIABLO expression.
Hypothesis-generating for Smac/DIABLO-mediated synergy in laryngeal carcinoma; leaves clinical translation open pending in vivo validation.
AIMS AND BACKGROUND: The major obstacles for tumor chemotherapy are drug resistance and/or adverse effects on the host. In the present study we investigated the role of the second mitochondria-derived activator of caspase (Smac/DIABLO) in the action of cisplatin (DDP), 5-fluorouracil (5-FU), and the combination of both in Hep-2 cells. METHODS AND STUDY DESIGN: Hep-2 laryngeal carcinoma cells exposed to DDP, 5-FU and the combination of both were investigated. Cell viability was determined by MTT assay. Apoptosis was measured by Ho.33342 and PI double staining and flow cytometry. The expression of Smac/DIABLO at the mRNA and protein level was assayed by RT-PCR and Western blotting. RESULTS: DDP, 5-FU and the combination of both drugs reduced the cell survival rates in a concentration- and time-dependent manner. The drug combination not only exerted a stronger inhibitory effect, but also at a lower concentration compared with the single drugs. Apoptosis was concomitant in a caspase-dependent manner. The expression of Smac/DIABLO increased significantly at both mRNA and protein levels after cell exposure to the combination compared with single drugs. CONCLUSIONS: Smac/DIABLO plays a pivotal role in attaining a synergistic effect in Hep-2 cells in response to this combined strategy.
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Lu et al. (2010) studied this question.
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