[Thrichosanthin enhances cisplatin-induced laryngocarcinoma apoptosis through inhibiting transcription factor nuclear...

To investigate the combined effect of thrichosanthin (TCS) and cisplatin on Hep-2 and AMC-HN-8 cell proliferation.

Hep-2 and AMC-HN-8 cells were treated with low (3 µg/ml) or high (10 µg/ml) concentration of cisplatin (10 µg/ml), TCS(5 µg/ml), or the combination TCS (5 µg/ml) and cisplatin (3 µg/ml), the cells no exposure to the drugs as control. Cell proliferation was detected by CCK-8. Toxicity of drugs to cells was evaluated by LDH assay. Flow cytometry was used to detect apoptosis. Western blot was performed to detect the expressions of JNK, phosphor-JNK, p38, phosphor-p38, NF-κB, inhibitor of κB (I-κB), and phospho-I-κB.

Compared with TCS (5 µg/ml) or cisplatin (3 µg/ml) alone, the combination of them had more significant inhibitory effect on the proliferation of Hep-2 and AMC-HN-8 cells (P < 0.01), but with no significant increase in cytotoxicity (P > 0.05). Western blot showed the expression of p-JNK/SAPK significantly increased in the cells treated with 5 µg/ml TCS for 48 hours, while the expression of NF-κB and phospho-I-κB increased in the cells treated with 3 µg/ml cisplatin. However in the cells treated with 5 µg/ml TCS combined with 3 µg/ml cisplatin, the expression of p-JNK stayed at a high level and the expressions of NF-κB and phospho-I-κB decreased dramatically compared to the cells treated with 3 µg/ml cisplatin alone.

TCS could enhance cisplatin-induced apoptosis in Hep-2 and AMC-HN-8, at least in part, by inhibiting the NF-κB signaling pathway and activating JNK/SAPK signaling pathway and thus strengthening the antitumor effects of cisplatin, which highlights the possibility of combined application of TCS and cisplatin in the treatment of laryngeal carcinoma.