葡萄糖在细胞吸收硼酸及取代硼酸中的作用研究

Glucose regulates cellular uptake of boric acid and substituted boric acid

硼中子俘获治疗(boron neutron capture therapy,BNCT)是肿瘤治疗的一种二元体系,利用含^(10)B药物对肿瘤细胞的高选择性、在肿瘤细胞中有足够的富集量和滞留时间,用具有合适能量的超热中子束照射肿瘤部位,发生中子俘获反应^(10)B(n,α)^(7)Li,反应释放出的高传能线密度α粒子和7Li,在一个细胞大小范围杀死肿瘤细胞.因此,含^(10)B药物的高效、高选择性对肿瘤细胞的靶向输送是BNCT有效性提高的关键.为了提高肿瘤细胞对含硼化合物的吸收,本文基于糖类物质与硼酸及其衍生物的相互作用,以及糖类具有在肿瘤细胞中富集的性质,研究了葡萄糖对正常细胞和肿瘤细胞吸收硼酸及其衍生物的影响,探讨了利用糖类物质增加肿瘤细胞中^(10)B含量的可能性.研究结果表明,随着葡萄糖含量的增加,肿瘤细胞对硼酸及取代硼酸的吸收增加,而正常细胞的吸收增加不明显.此外,葡萄糖对硼化合物在细胞中的滞留无明显的影响.

Boron neutron capture therapy(BNCT)is a binary radiotherapeutic modality based on nuclear capture and fission reactions that occur when the stable isotope boron-10 is irradiated with neutrons to produce high energyαparticles.For this to be successful,about 20μg·g^(-1)of^(10)B(per weight of tumor)must be selectively delivered to tumor cells(≈10^(9)atoms·cell^(-1)),and enough neutrons must be absorbed to sustain a lethal^(10)B(n,α)7 Li capture reaction.Therefore the key to enhance effectiveness of BNCT is for^(10)B to be targeted to tumor cells efficiently and selectively.Carbohydrates are known to accumulate in tumor cells.Increased boron uptake in tumor cells is expected after introducing carbohydrates in the form of covalently-bonded complexes of boric acid or derivatives.It was found that the uptake of boric acid and derivatives by tumor cells increased with increasing concentrations of glucose,but glucose uptake by normal cells did not increase markedly.Glucose had no effect on cellular persistence of boron compounds.