Nuclear Medicine Unit, Department of Oncohaematology, Policlinico "Tor Vergata", Viale Oxford 81, 00133, Rome, Italy.
Department of Experimental Medicine, Tor Vergata Oncoscience Research (TOR), University of Rome Tor Vergata, Via Montpellier 01, 00133, Rome, Italy.
Mol Cell Biochem. 2022 Oct;477(10):2319-2326. doi: 10.1007/s11010-022-04439-8. Epub 2022 May 7.
The main aim of this preliminary in vitro study was to evaluate both the uptake of [Tc]Sestamibi into prostate cancer cells and the relationship among [Tc]Sestamibi bioaccumulation, cancer cells proliferation and apoptosis. An in vitro study in which PC3 prostate cancer cell line was cultured with increasing doses of decayed sestamibi has been developed. Specifically, PC3 cells were incubated with three different concentrations of [Tc]Sestamibi: 10 µg/mL, 1 µg/mL, and 0.1 µg/mL Expression of apoptotic caspase-3 and AIF, as well as the ultrastructure of PC3 cells, were evaluated at T0 and after 24, 48, 72, and 120 h following [Tc]Sestamibi incubation. Data here reported showed the bioaccumulation of sestamibi in prostate cancer cells. As concern the cancer cell homeostasis, the treatment of PC3 cells with [Tc]Sestamibi strongly influenced the cells proliferation. Indeed, a significant reduction in the number of mitosis was observed. Noteworthy, the accumulation of sestamibi in prostate cancer cells was associated with the appearance of morphological signs of apoptosis. The increase in AIF and caspase 3 expression in prostate cancer cells treated with 10 µg/mL of [Tc]Sestamibi confirmed that this radiopharmaceutical can trigger the apoptosis. To the best of our knowledge, this preliminary study reported for the first time in vitro data about the uptake of sestamibi in prostate cancer cells. The evidence about the accumulation of sestamibi in prostate cancer cells and its role in the apoptosis process could open new clinical perspectives on the use of this radiopharmaceutical in both the diagnosis and treatment of prostate cancers.
本初步体外研究的主要目的是评估 [Tc]Sestamibi 进入前列腺癌细胞的摄取情况以及 [Tc]Sestamibi 生物积累、癌细胞增殖和凋亡之间的关系。开发了一种体外研究,其中培养了具有放射性碘-123-美罗华(decayed sestamibi)的 PC3 前列腺癌细胞系。具体而言,将 PC3 细胞与三种不同浓度的 [Tc]Sestamibi 孵育:10μg/mL、1μg/mL 和 0.1μg/mL。在孵育 [Tc]Sestamibi 后 24、48、72 和 120 小时,评估凋亡半胱氨酸蛋白酶-3 和 AIF 的表达以及 PC3 细胞的超微结构。这里报道的数据显示了 sestamibi 在前列腺癌细胞中的生物积累。关于癌细胞的内稳态,用 [Tc]Sestamibi 处理 PC3 细胞强烈影响细胞增殖。事实上,观察到有丝分裂的数量显著减少。值得注意的是,在前列腺癌细胞中 sestamibi 的积累与凋亡的形态学迹象的出现有关。用 10μg/mL 的 [Tc]Sestamibi 处理的前列腺癌细胞中 AIF 和半胱氨酸蛋白酶 3 表达的增加证实了这种放射性药物可以触发细胞凋亡。据我们所知,这项初步研究首次在体外报告了 sestamibi 在前列腺癌细胞中的摄取数据。关于 sestamibi 在前列腺癌细胞中的积累及其在凋亡过程中的作用的证据可能为放射性药物在前列腺癌的诊断和治疗中的应用开辟新的临床前景。