Cervical Cancer HeLa Cell Autocrine Apoptosis Induced by Coimmobilized IFN-γ plus TNF-α Biomaterials

作者：Jian Li, Yuxiao Zhang, Liyi Chen, Xinhua Lu, Zhibin Li, Yongyong Xue, Yan‐Qing Guan · 发表于：ACS Applied Materials & Interfaces · 年份：2018 · DOI：10.1021/acsami.7b18277 · 被引用次数：23 · 研究领域：RNA Interference and Gene Delivery、interferon and immune responses、Immune Response and Inflammation

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 Fe 3 O 4 –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.