The Experimental Study Of Therapy Of Liver Metastasis From Human Colon Cancer With Arsenic Troxide In Nude Mice

Colorectal cancer is one of the malignancies with the highest frequency in our country. The liver is the first place that colorectal cancer will metastases through vessels. Metastatic liver disease is the commonest cause of death in patients with colorectal cancer. Although surgical resection is the first choice in treatment of liver metastasis from colorectal cancer, Chemotherapy is necessary for most patients. With the study in the relationship between cancer and apoptosis, it was proved that cancer could be treated with apoptosis. Recently, scientists in our country cured patients with acute promyelocytic leukemia (APL) by arsenic trioxide (As2O3) successfully. Studies suggested that apoptosis was the mechanism. Followed studies suggested that not only APL but also many other tumors could occur apoptosis after treated with As2O3. Apoptosis is controlld by genes. Bcl-2 is one of the most important genes concerned with apoptosis. It could prolong survival period of many cells. It could enhance the chance to acquire genes with defect. Bcl-2 is concerned with many kinds of cancers. Bax is another important gene in the bcl-2 family. It could induce apoptosis through depressing the function of bcl-2. The ratio of bcl-2 and bax could decide the cell's fate, survival or apoptosis.In this experimental study, LS-174T cell line and nude mice model of liver metastasis from colon cancer were treated with As2O3 to observe the inhibition of proliferation and the induction of apoptosis by it. The therapeutic effect of As2O3 to human colon adenocarcinoma liver metastases was evaluated by comparison with 5-Fu and epirubicin. The bcl-2 and bax protein in LS-174T cell line and metastatic cancer were detected byimmunohistochemical staining. The results and conclusions were as follows:1. As2O3 could significantly inhibit the proliferation of LS-174T cell and induce it to apopotosis.2. As2O3 could make efficient therapy to the nude mice with liver metestasis. The survival period of tumor-loading nude mice was prolonged. The numbers of hepatic metastatic lesions and the proliferation index (PI) decreased. The level of CEA in serum and ascites was also lowered in the treated group. The therapeutic effect of As2O3 was equivalent to 5-Fu and epirubicin.3. After treated with As2O3, the bcl-2 was down-regulated while bax was up-regulated in the cell line. In the metastatic tumor of the treated animals, the bcl-2 was down-regulated and bax was up-regulated too.These results suggest that As2O3 can obviously inhibit the proliferation of LS-174T by inducing cell apoptosis depending on the dose and time. As2O3 can make efficient therapy to the nude mice with liver metestasis. The therapeutic effect of As2O3 is equivalent to 5-Fu and epirubicin. After treated with As2O3, the bcl-2 is down-regulated while bax is up-regulated in the cell line and in the metastatic tumor.