Andersson Jennie, Rosestedt Maria, Orlova Anna
Department of Medicinal Chemistry, Preclinical PET Platform, Uppsala University, Uppsala 751 83, Sweden.
Oncol Lett. 2015 Feb;9(2):950-954. doi: 10.3892/ol.2014.2760. Epub 2014 Dec 3.
Prostate cancer (PCa) is the most common type of cancer among males. Human epidermal growth factor receptor type 2 (HER2) expression in PCa has been reported by several studies and its involvement in the progression towards androgen-independent PCa has been discussed. External irradiation is one of the existing therapies, which has been demonstrated to be efficient in combination with androgen deprivation therapy for the treatment of advanced PCa. However, 20-40% of patients develop recurrent and more aggressive PCa within 10 years. The current study investigates the involvement of HER2 in survival and radioresistance in PCa cells and we hypothesized that, by monitoring HER2 expression, treatment may be personalized. The PCa cell lines, LNCap, PC3 and DU-145, received a 6 Gy single dose of external irradiation. The number of PC3 cells was not affected by a single dose of radiation, whereas a 5-fold decrease in cell number was detected in LNCap (P<0.00001) and DU-145 (P<0.0001) cells. The HER2 expression in PC3 exhibited a significant increase post irradiation, however, the expression was stable in the remaining cell lines. The administration of trastuzumab post-irradiation resulted in a 2-fold decrease in the PC3 cell number, while the drug did not demonstrate additional effects in LNCap and DU-145 cells, when compared with that of irradiation treatment alone. The results of the present study demonstrated that an increase in membranous HER2 expression in response to external irradiation may indicate cell radioresistance. Furthermore, imaging of HER2 expression prior to and following external irradiation may present a step towards personalized therapy in PCa.
前列腺癌（PCa）是男性中最常见的癌症类型。多项研究报道了PCa中人类表皮生长因子受体2（HER2）的表达情况，并讨论了其在向雄激素非依赖性PCa进展过程中的作用。外照射是现有的治疗方法之一，已证明其与雄激素剥夺疗法联合使用对晚期PCa的治疗有效。然而，20%-40%的患者在10年内会出现复发性且更具侵袭性的PCa。本研究调查了HER2在PCa细胞存活和放射抗性中的作用，我们假设，通过监测HER2表达，治疗可能实现个性化。PCa细胞系LNCap、PC3和DU-145接受了6 Gy的单次外照射剂量。PC3细胞的数量不受单次辐射剂量的影响，而在LNCap细胞（P<0.00001）和DU-145细胞（P<0.0001）中检测到细胞数量减少了5倍。PC3中HER2的表达在照射后显著增加，然而，在其余细胞系中表达稳定。照射后给予曲妥珠单抗导致PC3细胞数量减少了2倍，而与单独的照射治疗相比，该药物在LNCap和DU-145细胞中未显示出额外的效果。本研究结果表明，对外照射的反应中膜性HER2表达的增加可能表明细胞放射抗性。此外，外照射前后HER2表达的成像可能是PCa个性化治疗的一个步骤。
