AIM: To evaluate the effects of p53 on apoptosis and proliferation of hepatocellular carcinoma (HCC) cells treated with transcatheter arterial chemoembolization (TACE).

METHODS: A total of 136 patients with HCC received TACE and other management before surgery were divided into TACE group and non-TACE group. TACE group included 79 patients who had 1-5 courses of TACE before surgery, of them, 11 patients had 1-4 courses of chemotherapy (group A), 33 patients had 1-5 courses of chemotherapy combined with iodized oil (group B), 23 patients had 1-3 courses of chemotherapy, iodized oil and gelatin sponge (group C), 12 patients had 1-3 courses of chemotherapy combined with iodized oil, ethanol and gelatin sponge (group D). Non-TACE group included the remaining 57 patients who had surgery only. The extent of apoptosis was analyzed by transferase mediated dUTP nick end labeling (TUNEL) staining. The expressions of p53, Bcl-2, Bax, Ki-67 and PCNA protein were detected by immunohistochemical method.

RESULTS: p53 protein expressions in trabecular and clear cells in HCC specimens were significantly lower than that in pseudoglandar, solid, poorly differentiated or undifferentiated and sclerosis HCC (P < 0.05). Expression of p53 protein in HCC cells increased with the increase of pathological grades (P < 0.05), and correlated positively with expressions of Ki-67 and PCNA protein, and negatively with Bcl-2 to Bax protein expression rate and AI (P < 0.05). Expression of p53 protein was significantly higher in group A than in groups B, C, D and the non-TACE group, and was higher in group B than in groups C and D, and lower in group D than in the non-TACE group (P < 0.05).

CONCLUSION: Expression of p53 protein can enhance proliferation of HCC cells and suppress apoptosis of HCC cells after TACE.

• Adult
• Aged
• Apoptosis/physiology
• Carcinoma, Hepatocellular/metabolism
• Carcinoma, Hepatocellular/pathology
• Carcinoma, Hepatocellular/therapy
• Cell Division/physiology
• Chemoembolization, Therapeutic
• Female
• Humans
• Immunohistochemistry
• In Situ Nick-End Labeling
• Ki-67 Antigen/metabolism
• Liver Neoplasms/metabolism
• Liver Neoplasms/pathology
• Liver Neoplasms/therapy
• Male
• Middle Aged
• Proliferating Cell Nuclear Antigen/metabolism
• Proto-Oncogene Proteins/metabolism
• Proto-Oncogene Proteins c-bcl-2/metabolism
• Tumor Suppressor Protein p53/metabolism
• bcl-2-Associated X Protein

AIM: To investigate the correlation between lymphogenous metastasis and matrix metalloproteinases (MMPs) activity and the expression of Fas ligand of tumor cells in lymph nodes.

METHODS: Fifty-six inbred 615-mice were equally divided into 2 groups and inoculated with Hca-F and Hca-P cells. Their lymph node metastatic rates were examined. Growth fraction of lymphocytes in host lymph nodes was detected by flow cytometry. The Hca-F and Hca-P cells were cultured with extract of lymph node, liver or spleen. The quantity of MMPs in these supernatants was examined by zymographic analysis. The expression of Fas ligand, PCNA, Bcl-2 protein of Hca-F and Hca-P cells in the mice were examined by immunohistochemistry. The apoptosis signals of macrophages in lymph nodes were observed with in situ DNA fragmentation.

RESULTS: On the 28^th day post-inoculation, the lymph node metastatic rate of Hca-F was 80% (16/20), whereas that of Hca-P was 25% (5/20). The growth fraction of lymphocytes was as follows: in the Hca-F cells, the proliferating peak of lymphocytes appeared on the 14^th day post-inoculation and then decreased rapidly, while in Hca-P cells, the peak appeared on the 7^th day post inoculation and then kept at a high level. With the extract of lymph node, the quantity of the MMP-9 activity increased (P < 0.01) and active MMP-9 and MMP-2 were produced by both Hca-F and Hca-P tumor cells, which did not produce MMPs without the extract of lymph node or with the extracts of the liver and spleen. The expression of Fas Ligand of Hca-F cells was stronger than that of Hca-P cells (P < 0.01). The expressions of PCNA and Bcl-2 protein of Hca-F cells in the tumors of inoculated area were the same as that of Hca-P cells. In situ DNA fragmentation showed that the positive signals of macrophages were around Hca-F cells.

CONCLUSION: Secretion of MMPs which was associated with metastatic ability of Hca-F and Hca-P tumor cells depends on the environment of lymph nodes. The increased expression of Fas ligand protein of Hca-F tumor cells with high lymphogenous metastatic potential in lymph nodes may help tumor cells escape from being killed by host lymphocytes.

• liver neoplasms/pathology
• lymphatic metastasis
• tumor cells, cultured
• metalloproteinases/secretion

• Animals
• DNA Fragmentation
• Fas Ligand Protein
• Flow Cytometry
• Liver Neoplasms, Experimental/chemistry
• Liver Neoplasms, Experimental/metabolism
• Liver Neoplasms, Experimental/secondary
• Lymph Nodes/enzymology
• Lymph Nodes/pathology
• Lymphatic Metastasis
• Macrophages/pathology
• Matrix Metalloproteinase 2/metabolism
• Matrix Metalloproteinase 9/metabolism
• Membrane Glycoproteins/analysis
• Mice
• Mice, Inbred Strains
• Tumor Cells, Cultured