Partial hepatectomy is currently one of the important methods for the treatment of primary liver cancer, but postoperative recurrence and metastasis have been troubling the medical community, and Kondo M suggested that Cox-2 may have an important role in the recurrence of hepatocellular carcinoma after resection. At present, local interventional therapy is increasingly applied to patients with hepatocellular carcinoma, but the long-term efficacy is not satisfactory, with high recurrence and metastasis rates and poor prognosis. Tang Wubing et al. used immunohistochemistry to detect the changes of COX-2 expression in hepatocellular carcinoma tissues before and after hepatic artery chemoembolization (TACE), and the results showed that COX-2 expression was enhanced after TACE for hepatocellular carcinoma, suggesting that the selection of specific COX-2 inhibitors along with hepatic artery chemotherapy for hepatocellular carcinoma patients may improve the long-term efficacy of hepatocellular carcinoma interventions. The Cox-2 signaling pathway plays an important role in the development of primary hepatocellular carcinoma, mainly in tumor cell infiltration, proliferation, apoptosis, angiogenesis, etc. The transcriptional control of Cox-2 gene is cell-specific, and multiple signaling pathways jointly regulate the expression of Cox-2. Cox-2 expression is also inhibited by glucocorticoids, some interleukins, and anti-inflammatory factors. Recent studies have shown that both hepatitis viruses enhance Cox-2 expression. After integration of hepatitis B virus DNA into the host genome, the viral protein HBx activates the Cox-2 promoter via an associated transcript, which in turn regulates Cox-2 expression; hepatitis C virus activates NF-kB, which regulates Cox-2 expression. Cox-2 inhibitors have been playing an important role in the prevention and treatment of tumors. Epidemiological surveys have shown that patients with colorectal cancer taking non-steroidal anti-inflammatory drugs (NSAIDs) can reduce mortality by 40% – 50% compared to not taking the drug. However, there are no definite data on the effect on hepatocellular carcinoma.Ji Yeon Baek confirmed that NS-398, a selective Cox-2 inhibitor, inhibited the growth of HuH7 and HepG2 in hepatocellular carcinoma cells in a dose- and time-dependent manner.The drug inhibited cell proliferation by arresting cell division in the G1 phase, but it was not found to induce apoptosis.Michael Andre Kern Selective Cox-2 inhibitors have been shown to inhibit the growth of primary hepatocellular carcinoma in nude mice in vivo. Numerous research results have suggested that blocking the Cox-2-mediated signaling pathway may be effective in preventing and treating hepatocellular carcinoma, and Cox-2 may become a new target for hepatocellular carcinoma treatment. Primary liver cancer and TNF-α Professor Bharat B. Aggarwal first isolated tumor necrosis factor (TNF-α) as an “anti-cancer cytokine” in 1984, but found that it can cause and promote cancer development. When stimulated by pathogenic factors, it induces other inflammatory regulators and proteases in response to the inflammatory response. Studies have demonstrated that TNF-α can also be produced by tumors and, as an endogenous promoter, has been linked to multiple aspects of tumor development, including tumor cell formation, escape, proliferation, infiltration, angiogenesis, and metastasis. Many tumors can produce TNF-α, such as B-lymphocytoma, acute leukemia, colon cancer, breast cancer, pancreatic cancer, and squamous cell carcinoma. Most TNF-α in vivo acts as an autocrine growth factor to promote tumor growth, and in some tumors, it regulates tumor growth by inducing the expression of other growth factors. lin W and Fukata M demonstrated in vivo in animals and in cancer cells, respectively, that many inflammatory mediators, including TNF-α and interleukin (IL-6), can stimulate tumor growth and promote tumor progression. In the study of primary liver cancer, most experts believe that TNF-α plays a role in tumorigenesis and progression through the nuclear transcription factor NF-kB pathway. pikarsky E believes that TNF-α activates intracellular nuclear factor-kappaB (NF-kB) in hepatocytes, which not only accelerates cellular mutation and leads to “crazy” cancer cell ” growth, but also assists such mutated cells to escape from the initial tumor and metastasize to other parts of the body. Bai Li confirmed through animal experiments that the expression of inflammatory cytokines, especially TNF-α, has a significant positive correlation with liver cancer metastasis and may have an enhancing effect on tumor metastasis. Primary liver cancer and NF-kB Eukaryotic nuclear transcription factor-kappaB (NF-kB) broadly regulates the expression of a range of human genes, especially immune response, inflammatory response, virus-related genes and proto-oncogenes. Malignant transformation of normal cells is predicated on sustained stimulation of positive growth signals or blocked apoptosis. Studies have shown that NF-kB signaling pathway is closely related to tumorigenesis, and there are two possible pathways: one is the activation of external tumorigenic factors followed by regulation of cell cycle D1 (CyclinD1) overexpression, which can shorten the G1 phase and promote cells to enter the proliferative phase, thus promoting cell transformation; the other is the inhibition of pro-apoptotic factors, thus protecting cells from apoptosis. Studies have demonstrated that NF-kB plays a role in inducing cell transformation, promoting cell proliferation, angiogenesis, infiltration and metastasis, and is involved in the process of multiple tumorigenesis, development and regression. Studies on the relationship between tumors and inflammation have shown that most inflammatory factors act by activating NF-kB and most anti-inflammatory factors inhibit NF-kB activity. Similarly, most oncogenes and tumor-promoting factors activate NF-kB, while chemopreventive factors inhibit it. Part of the mechanism of primary liver cancer and NF-kB has been elucidated. in an article published in Nature, Pikarsky et al. demonstrated that: inflammation induced hepatic NF-kB expression, no hepatitis occurred when NF-kB was blocked in mice from birth to 7 months, and hepatocarcinoma did not occur when NF-kB was inhibited during hepatocarcinogenesis, and the degree of hepatitis was reduced and NF-kB expression was not present when mice were fed nonsteroidal anti-inflammatory drugs for 10 days. LiQ concluded that hepatitis virus infection stimulates NF-kB expression and enhances its DNA-binding capacity, and intracellular NF-kB activation is associated with abnormal hepatocellular carcinogenesis. The abnormal activation of intracellular NF-kB is closely related to the development of primary liver cancer. Our experiments confirmed (results not yet published) that NF-kB was positively expressed in the nucleus of liver cancer tissues in a focal pattern and in the nucleus of peri-cancerous tissues in a small amount, suggesting that NF-kB may enter the nucleus after activation and exert its transcriptional activity, thus participating in the development of liver cancer. kB involvement in the development of hepatocellular carcinoma may be related to angiogenesis, and inhibition of NF-kB activity may become a new target for tumor gene therapy. Cheng-Jun Zheng et al. also demonstrated that NF-kB and VEGF expression were positively correlated in hepatocellular carcinoma, and VEGF could promote hepatocellular carcinoma growth and invasion and metastasis, while NF-kB had a role in promoting VEGF expression upregulation in tumor growth. The research on the relationship between NF-kB and inflammation and cancer has become a hot topic, and with the in-depth research, NF-kB and the proteins of its pathway will become a new target for the prevention and treatment of malignant tumors. NF-kB inhibitors for the treatment of tumors are currently in clinical trials. Primary liver cancer and complement Traditionally, the complement system is an important part of the innate immune system and one of the main mechanisms by which antibodies exert their immune effects, with a variety of biological functions such as killing bacteria, lysing viruses, mediating inflammation, and regulating the immune response. Ostrand-Rosenberg S et al. published in Cell that whether the immune system inhibits or promotes tumor growth depends on the balance between the two. maciej M suggested that the complement system may promote tumor growth by helping tumor cells to escape immunity, and tumor cells may be protected from organismal attack by the complement system. Although the role of the complement system in malignancy is not fully defined, Divergent Bovine Bacteria and BCG have been successfully used in clinical treatment of malignancy, providing successful examples of complement and inflammation in the treatment of tumors. Studies on the relationship between the complement system and tumors have further confirmed the possible close link between inflammation and cancer. Many researchers are currently studying the activation of complement as a complement to tumor antibody immunotherapy, and the combination of complement-related drugs and anti-tumor vaccines may provide a proven approach for patients with advanced malignancies. Metastasis, Recurrence and Inflammation in Primary Liver Cancer The main reason for treatment failure in primary liver cancer is the inability to control postoperative recurrence, and the root cause of liver cancer metastasis is the alteration of cytogenetic characteristics. Inflammation promotes tumorigenesis, progression and metastasis. Partial hepatectomy or liver transplantation is a traumatic process for the body and can cause an inflammatory response in the liver or throughout the body. The inflammatory response of the liver, whether due to viral infection or surgical trauma, is strongly associated with the development and postoperative recurrence of hepatocellular carcinoma. Hepatitis activity, viral load, and liver function reserve are independent risk factors for postoperative primary hepatocellular carcinoma. The recurrence rate of primary hepatocellular carcinoma after surgery is significantly higher in concomitant hepatitis and cirrhosis, and the degree of inflammatory response in the liver itself directly or indirectly plays a role in promoting tumor recurrence. Several studies have shown that primary hepatocellular carcinoma without viral infection has a better prognosis compared with primary hepatocellular carcinoma with viral infection in the former. Bai Li et al. applied an experimental liver metastasis model to confirm that surgery, especially partial hepatectomy, promotes liver cancer metastasis and is positively correlated with the degree of metastasis, and suggests that postoperative metastasis of liver cancer may be related to traumatic factors favoring the adhesion of tumor cells. Currently, targeted drugs have achieved remarkable efficacy in tumor treatment, and bevacizumab, erlotinib, and sorafenib have been used in the clinical trial stage of hepatocellular carcinoma treatment. We study the relationship between inflammation and hepatocellular carcinoma, and explore the mechanism of the promoting effect of inflammatory mediators on the occurrence and metastasis of hepatocellular carcinoma. The ultimate goal is to inhibit or slow down the occurrence and development of primary hepatocellular carcinoma, reduce the recurrence and metastasis of hepatocellular carcinoma, improve the postoperative cure rate of hepatocellular carcinoma, and prolong the survival of hepatocellular carcinoma patients by discovering the mechanism of action between the two.