He. Kim et al., Neutron radiation enhances cisplatin cytotoxicity independently of apoptosis in human head and neck carcinoma cells, CLIN CANC R, 6(10), 2000, pp. 4142-4147
Recent advances in combined modality treatment of locally advanced head and
neck cancer have improved local and regional disease control and survival
with better functional outcome, However, the local and regional failure rat
e after radiation therapy is still high for tumors that respond poorly to c
isplatin-based neoadjuvant chemotherapy. This clinical observation suggests
a common biological mechanism for resistance to cisplatin and photon irrad
iation. In this report, we investigated the molecular basis underlying cisp
latin resistance in head and neck squamous carcinoma (HNSCC) cells and aske
d if fast neutron radiation enhances cisplatin cytotoxicity in cisplatin-re
sistant cells, We found that cisplatin sensitivity correlates with caspase
induction, a cysteine proteinase family known to initiate the apoptotic cel
l death pathway, suggesting that apoptosis may be a critical determinant fo
r cisplatin cytotoxicity, Neutron radiation effectively enhanced cisplatin
cytotoxicity in HNSCCs including cisplatin-resistant cells, whereas photon
radiation had little effect on cisplatin cytotoxicity. Interestingly, neutr
on-enhanced cisplatin cytotoxicity was associated neither with apoptosis no
r with cell cycle regulation, as determined by caspase activity assay, anne
xin V staining, and flow cytometric analysis, Taken together, the present s
tudy provides a molecular insight into cisplatin resistance and may also pr
ovide a basis for more effective multimodality protocols involving neutron
radiation for patients with locally advanced head and neck cancer.