Role of p53 mutation in the effect of boron neutron capture therapy on oral squamous cell carcinoma

Abstract

BackgroundBoron neutron capture therapy (BNCT) is a selective radiotherapy, being effective for the treatment of even advanced malignancies in head and neck regions as well as brain tumors and skin melanomas. To clarify the role of p53 gene, the effect of BNCT on oral squamous cell carcinoma (SCC) cells showing either wild- (SAS/neo) or mutant-type (SAS/mp53) p53 was examined.MethodsCells were exposed to neutron beams in the presence of boronophenylalanine (BPA) at Kyoto University Research Reactor. Treated cells were monitored for modulations in colony formation, proliferation, cell cycle, and expression of cell cycle-associated proteins.ResultsWhen SAS/neo and SAS/mp53 cells were subjected to BNCT, more suppressive effects on colony formation and cell viability were observed in SAS/neo compared with SAS/mp53 cells. Cell cycle arrest at the G1 checkpoint was observed in SAS/neo, but not in SAS/mp53. Apoptotic cells increased from 6 h after BNCT in SAS/neo and 48 h in SAS/mp53 cells. The expression of p21 was induced in SAS/neo only, but G2 arrest-associated proteins including Wee1, cdc2, and cyclin B1 were altered in both cell lines.ConclusionThese results indicate that oral SCC cells with mutant-type are more resistant to BNCT than those with wild-type p53, and that the lack of G1 arrest and related apoptosis may contribute to the resistance. At a physical dose affecting the cell cycle, BNCT inhibits oral SCC cells in p53-dependent and -independent manners.

Induction of multinucleation in oral squamous cell carcinoma tissue with mutated p53 surviving boron neutron capture therapy

“…Thus, the cell cycle of SAS/neo tumours seems to be arrested at G2 in response to BNCT. This result is consistent with our previous findings indicating that SAS and SAS/neo cells were arrested at the G2 checkpoint after BNCT in culture (Kamida et al 2008, Fujita et al 2009). In untreated SAS/mp53 tumours, the expression of Wee1, cyclin B1 and phosphorylation of cdc2 were maintained at high levels.…”

Apoptosis through Bcl-2/Bax and Cleaved Caspase Up-Regulation in Melanoma Treated by Boron Neutron Capture Therapy

“…These data confirm apoptosis after BNCT, as also noted by Masunaga [20], [21], Wang [32] and Fujita [43], who observed apoptosis in vitro and in vivo in mouse lymphoma, glioma and oral squamous cell carcinoma, respectively. Some authors report that BNCT apoptosis may be specific to some tumor types, for example, Aromando [33] and Kamida [44], who studied hamster cheek pouch tumor and human oral squamous cell carcinoma xenografts, respectively.…”

Enhancing effect of ultrasound on boron concentrations in an oral squamous cell carcinoma cell line SAS for boron neutron capture therapy

“…Previously, we performed BNCT for monolayer cultures of oral SCC cell lines, SAS and FI, in flasks, in which cells were incubated with BPA or BSH and then exposed to thermal neutrons [27,28,32]. However, this time, cells treated with boron compounds were exposed to ultrasound and then thermal neutrons.…”