Grosche Sinja, Bogdanova Natalia V, Ramachandran Dhanya, Lüdeking Marcus, Stemwedel Katharina, Christiansen Hans, Henkenberens Christoph, Merten Roland
Radiation Oncology Research Unit, Hannover Medical School, Hannover, Germany.
Gynaecology Research Unit, Medical School, Hannover, Germany.
Front Oncol. 2022 Oct 27;12:852694. doi: 10.3389/fonc.2022.852694. eCollection 2022.
Breast cancer (BC) is one of the most diagnosed malignant carcinomas in women with a triple-negative breast cancer (TNBC) phenotype being correlated with poorer prognosis. Fractionated radiotherapy (RT) is a central component of breast cancer management, especially after breast conserving surgery and is increasingly important for TNBC subtype prognosis. In recent years, moderately hypofractionated radiation schedules are established as a standard of care, but many professionals remain skeptical and are concerned about their efficiency and side effects. In the present study, two different triple-negative breast cancer cell lines, a non-malignant breast epithelial cell line and fibroblasts, were irradiated daily under normofractionated and hypofractionated schedules to evaluate the impact of different irradiation regimens on radiation-induced cell-biological effects. During the series of radiotherapy, proliferation, growth rate, double-strand DNA break-repair (DDR), cellular senescence, and cell survival were measured. Investigated normal and cancer cells differed in their responses and receptivity to different irradiation regimens, indicating cell line/cell type specificity of the effect. At the end of both therapy concepts, normal and malignant cells reach almost the same endpoint of cell count and proliferation inhibition, confirming the clinical observations in the follow-up at the cellular level. These result in cell lines closely replicating the irradiation schedules in clinical practice and, to some extent, contributing to the understanding of growth rate or remission of tumors and the development of fibrosis.
乳腺癌（BC）是女性中最常被诊断出的恶性肿瘤之一，三阴性乳腺癌（TNBC）表型与较差的预后相关。分割放疗（RT）是乳腺癌治疗的核心组成部分，尤其是在保乳手术后，对TNBC亚型的预后越来越重要。近年来，适度超分割放疗方案已成为标准治疗方法，但许多专业人士仍持怀疑态度，并担心其疗效和副作用。在本研究中，对两种不同的三阴性乳腺癌细胞系、一种非恶性乳腺上皮细胞系和成纤维细胞，按照常规分割和超分割方案进行每日照射，以评估不同照射方案对辐射诱导的细胞生物学效应的影响。在一系列放疗过程中，测量细胞增殖、生长速率、双链DNA断裂修复（DDR）、细胞衰老和细胞存活情况。研究发现，正常细胞和癌细胞对不同照射方案的反应和敏感性不同，表明存在细胞系/细胞类型特异性效应。在两种治疗方案结束时，正常细胞和恶性细胞的细胞计数和增殖抑制终点几乎相同，在细胞水平上证实了随访中的临床观察结果。这些结果在细胞系中密切复制了临床实践中的照射方案，并在一定程度上有助于理解肿瘤的生长速率或缓解情况以及纤维化的发展。
