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

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-alpha is frequently used in tumor biotherapy while IFN-gamma can directly inhibit tumor cell proliferation. In our study, TNF-alpha and IFN-gamma were coimmobilized on polystyrene material (PSt) or Fe3O4-oleic acid nanoparticles (NPs). Then the structural change of these two proteins can be observed. Meanwhile, the expressions of both TNF-alpha and IFN-alpha increased significantly, as determined by gene microarray analysis; however, in the presence of TNF-alpha plus IFN-alpha inhibitors, TNF-alpha and IFN-alpha did not increase in HeLa cells induced by coimmobilized IFN-gamma plus TNF-alpha. Our results indicate that such change can stimilate HeLa cells to secrete more TNF-alpha and IFN-alpha, 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-gamma plus TNF-alpha has apparent effects for cancer treatment in vivo, which is of great significance for translation into clinical medicine.