Tang Chao, Wang Jin, Wei Qi, Du Yi-Peng, Qiu He-Ping, Yang Chao, Hou Yu-Chuan
Department of Urology, The First Hospital of Jilin University, Changchun, Jilin 130021, P.R. China.
Department of Anesthesiology, The First Hospital of Jilin University, Changchun, Jilin 130021, P.R. China.
Oncol Lett. 2018 May;15(5):7060-7068. doi: 10.3892/ol.2018.8204. Epub 2018 Mar 7.
Tropomyosin-1 (TPM1), a widely expressed actin-binding protein, is downregulated in many tumors and associated with cancer progression. A previous study from our group suggested that TPM1 could be involved in renal cell carcinoma (RCC) apoptosis, but the mechanisms and details remained unknown. The present study aimed to further examine the proapoptotic effects of TPM1 and investigate the underlying mechanisms in RCC cell lines. Results from cell viability, DAPI staining and apoptosis assays demonstrated that TPM1 upregulation inhibited cell proliferation and promoted cell apoptosis in both 786-O and ACHN RCC cell lines. However, TPM1 knockdown in the two RCC cell lines did not result in the opposite effects on cell proliferation or cell apoptosis. Comet assay and western blotting results demonstrated that TPM1 overexpression induced DNA damage and decreased the expression levels of the antiapoptotic factor BCL2 apoptosis regulator, while increasing the expression levels of the proapoptotic factors BCL2 associated X, Caspase-3 and p53 in 786-O and ACHN cells. The present findings suggest that TPM1 overexpression in RCC cell lines can induce tumor cell apoptosis via the p53-mediated mitochondrial pathway. Further studies are needed to fully elucidate the potential of TPM1 as a candidate for RCC targeted therapy in the future.
原肌球蛋白-1（TPM1）是一种广泛表达的肌动蛋白结合蛋白，在许多肿瘤中表达下调，并与癌症进展相关。我们团队之前的一项研究表明，TPM1可能参与肾细胞癌（RCC）的凋亡，但具体机制和细节尚不清楚。本研究旨在进一步研究TPM1的促凋亡作用，并探讨其在RCC细胞系中的潜在机制。细胞活力、DAPI染色和凋亡检测结果表明，TPM1的上调抑制了786-O和ACHN RCC细胞系的细胞增殖并促进了细胞凋亡。然而，在这两种RCC细胞系中敲低TPM1并未对细胞增殖或细胞凋亡产生相反的影响。彗星试验和蛋白质印迹结果表明，TPM1的过表达诱导了DNA损伤，并降低了抗凋亡因子BCL2凋亡调节蛋白的表达水平，同时增加了促凋亡因子BCL2相关X蛋白、半胱天冬酶-3和p53在786-O和ACHN细胞中的表达水平。本研究结果表明，RCC细胞系中TPM1的过表达可通过p53介导的线粒体途径诱导肿瘤细胞凋亡。未来需要进一步研究以充分阐明TPM1作为RCC靶向治疗候选药物的潜力。
