MOE Key Laboratory of Laser Life Science & Institute of Laser Life Science, College of Biophotonics , South China Normal University , Guangzhou 510631 , China.
Joint Laboratory of Laser Oncology with Cancer Center of Sun Yet-sen University , South China Normal University , Guangzhou 510631 , China.
ACS Appl Mater Interfaces. 2018 Mar 14;10(10):8451-8464. doi: 10.1021/acsami.7b18277. Epub 2018 Mar 2.
Using external methods to induce the death of cancer cells is recognized as one of the main strategies for cancer treatment. Research indicated that TNF-α is frequently used in tumor biotherapy while IFN-γ can directly inhibit tumor cell proliferation. In our study, TNF-α and IFN-γ were coimmobilized on polystyrene material (PSt) or FeO-oleic acid nanoparticles (NPs). Then the structural change of these two proteins can be observed. Meanwhile, the expressions of both TNF-α and IFN-α increased significantly, as determined by gene microarray analysis; however, in the presence of TNF-α plus IFN-α inhibitors, TNF-α and IFN-α did not increase in HeLa cells induced by coimmobilized IFN-γ plus TNF-α. Our results indicate that such change can stimilate HeLa cells to secrete more TNF-α and IFN-α, by which the apoptosis of HeLa cells could be further induced. This study is the first report of autocrine-induced apoptosis of HeLa cells. In addition, we performed ELISA, RT-PCR, flow cytometry, and Western blot analyses, as well as a series of analytical tests at the animal level. our data also indicate that the PSt-coimmobilized IFN-γ plus TNF-α has apparent effects for cancer treatment in vivo, which is of great significance for translation into clinical medicine.
利用外部方法诱导癌细胞死亡已被认为是癌症治疗的主要策略之一。研究表明,TNF-α 常用于肿瘤生物治疗,而 IFN-γ 可直接抑制肿瘤细胞增殖。在我们的研究中,TNF-α 和 IFN-γ 被共固定在聚苯乙烯材料(PSt)或 FeO-油酸纳米颗粒(NPs)上。然后可以观察到这两种蛋白质的结构变化。同时,通过基因微阵列分析发现,TNF-α 和 IFN-α 的表达均显著增加;然而,在存在 TNF-α 加 IFN-α 抑制剂的情况下,共固定 IFN-γ 加 TNF-α 诱导的 HeLa 细胞中 TNF-α 和 IFN-α 并未增加。我们的结果表明,这种变化可以刺激 HeLa 细胞分泌更多的 TNF-α 和 IFN-α,从而进一步诱导 HeLa 细胞凋亡。这是首次报道 HeLa 细胞的自分泌诱导凋亡。此外,我们进行了 ELISA、RT-PCR、流式细胞术和 Western blot 分析,以及一系列动物水平的分析测试。我们的数据还表明,PSt 共固定的 IFN-γ 加 TNF-α 对体内癌症治疗具有明显的效果,这对于转化为临床医学具有重要意义。