Clear cell renal cell carcinoma (ccRCC) is the most prevalent form of renal cancer and its treatment is hindered by a resistance to targeted therapies, immunotherapies and combinations of both. We have reported that the knockdown of the antisense noncoding mitochondrial RNAs (ASncmtRNAs) with chemically modified antisense oligonucleotides induces proliferative arrest and apoptotic death in tumor cells from many human and mouse cancer types. These studies have been mostly performed in vitro and in vivo on commercially available cancer cell lines and have shown that in mouse models tumor growth is stunted by the treatment. The present work was performed on cells derived from primary and metastatic ccRCC tumors. We established primary cultures from primary and metastatic ccRCC tumors, which were subjected to knockdown of ASncmtRNAs in vitro and in vivo in an orthotopic xenograft model in NOD/SCID mice. We found that these primary ccRCC cells are affected in the same way as tumor cell lines and in the orthotopic model tumor growth was significantly reduced by the treatment. This study on patient-derived ccRCC tumor cells represents a model closer to actual patient ccRCC tumors and shows that knockdown of ASncmtRNAs poses a potential treatment option for these patients.
透明细胞肾细胞癌（ccRCC）是最常见的肾癌类型，其治疗因对靶向疗法、免疫疗法及两者联合方案的耐药性而受到阻碍。我们既往研究发现，利用化学修饰的反义寡核苷酸敲低反义非编码线粒体RNA（ASncmtRNAs）可诱导多种人类和小鼠肿瘤细胞的增殖停滞与凋亡死亡。这些研究主要在商业可得的癌细胞系上开展体外及体内实验，并证实该处理能抑制小鼠模型的肿瘤生长。本研究采用源自原发性及转移性ccRCC肿瘤的细胞开展实验。我们建立了原发性和转移性ccRCC肿瘤的原代培养体系，并在NOD/SCID小鼠原位移植模型中进行了ASncmtRNAs的体外及体内敲低实验。研究发现这些原代ccRCC细胞与肿瘤细胞系呈现相同的效应模式，且在原位模型中该治疗能显著抑制肿瘤生长。这项基于患者来源ccRCC肿瘤细胞的研究构建了更接近真实患者ccRCC肿瘤的模型，表明ASncmtRNAs敲低技术为这类患者提供了潜在的治疗选择。
肿瘤(癌症)患者之家