Multifaceted role of NF-cB in hepatocellular carcinoma therapy: Molecular landscape, therapeutic compounds and nanomaterial approaches

The predominant kind of liver cancer is hepatocellular carcinoma (HCC) that its treatment have been trouble-some difficulties for physicians due to aggressive behavior of tumor cells in proliferation and metastasis. Moreover, stemness of HCC cells can result in tumor recurrence and angiogenesis occurs. Another problem is development of resistance to chemotherapy and radiotherapy in HCC cells. Genomic mutations participate in malignant behavior of HCC and nuclear factor-kappaB (NF-cB) has been one of the oncogenic factors in different human cancers that after nuclear translocation, it binds to promoter of genes in regulating their expression. Overexpression of NF-cB has been well-documented in increasing proliferation and invasion of tumor cells and notably, when its expression enhances, it induces chemoresistance and radio-resistance. Highlighting function of NF-cB in HCC can shed some light on the pathways regulating progression of tumor cells. The first aspect is proliferation acceleration and apoptosis inhibition in HCC cells mediated by enhancement in expression level of NF-cB. Moreover, NF-cB is able to enhance invasion of HCC cells via upregulation of MMPs and EMT, and it triggers angiogenesis as another step for increasing spread of tumor cells in tissues and organs. When NF-cB expression enhances, it stimulates chemoresistance and radio-resistance in HCC cells and by increasing stemness and population of cancer-stem cells, it can provide the way for recurrence of tumor. Overexpression of NF-cB mediates therapy resistance in HCC cells and it can be regulated by non-coding RNAs in HCC. Moreover, inhi-bition of NF-cB by anti-cancer and epigenetic drugs suppresses HCC tumorigenesis. More importantly, nano -particles are considered for suppressing NF-cB axis in cancer and their prospectives and results can also be utilized for treatment of HCC. Nanomaterials are promising factors in treatment of HCC and by delivery of genes and drugs, they suppress HCC progression. Furthermore, nanomaterials provide phototherapy in HCC ablation.

Automated summary

The treatment of hepatocellular carcinoma (HCC), the most common type of liver cancer, poses difficulties for physicians due to the aggressive behavior of tumor cells and their resistance to chemotherapy and radiotherapy. The overexpression of nuclear factor-kappaB (NF-kB) plays a significant role in promoting the proliferation, invasion, and angiogenesis of HCC cells, as well as inducing chemoresistance and radioresistance. Inhibiting NF-kB through non-coding RNAs or anti-cancer drugs can suppress HCC tumorigenesis, and nanoparticles show promise in delivering genes and drugs for HCC treatment, as well as providing phototherapy for HCC ablation.