Effect of phosphorus-32 glass microspheres on human hepatocellular carcinoma in nude mice

AIM: To study the effects of phosphorus-32 glass microspheres(^32P-GMS) on human hepatocellular carcinoma in nude mice. METHODS: Human liver cancer cell line was implanted into the dorsal subcutaneous tissue of 40 BALB/c nude mice. Then the 40 tumor-bearing BALB/c nude mice were allocated into treatment group (n=32) and control group (n=8). In the former group different doses of ^32P-GMS were injected into the tumor mass, while in the latter nonradioactive ^31P-GMS was injected into the tumor mass. The experimental animals were sacrificed on the 14th day. The ultrastructural changes of tumor in both treatment group and control group were studied with transmission electron microscopy (TEM) and stereology. RESULTS: In treatment group, a lot of tumor cells were killed and the death rate of tumor cells was much higher (35-70%). UItrastructurally, severe nuclear damage was observed in the death cells. The characteristics of appoptosis such as margination of heterochromatin was also found in some tumor cells. Besides, well differentiated tumor cells, degenerative tumor cells and some lymphocytes were seen. The skin and musde adjacent to the tumor were normal. In control group, the tumor consisted of poorly differentiated tumor cells, in which there were only a few of dead cells (5%). Stereologicl analysis of ultrastructral morphology showed that Vv of nuclei (53.31±3.46) and Vv of nucleoli (20.40±1.84) in the control group were larger than those (30.21±3.52 and 10.96±2.52) in the treatment group respectively (P<0.01), and Vv of RER (3.21±0.54) and Vv of mitochondria (4.53±0.89) in the control group were smaller than those (8.67±1.25 and 7.12±0.95) in the treatment group respectively (P<0.01, 0.05). Sv of the membrane of microvilli and canaliculi (27.12 um^2/100 um^3±11.84 um^2/100 um^3) in the control group was smaller than that (78.81 um^2/100 um^3±19.69 um^2/100 um^3) in the treatment group (P<0.01). But Vv of lipid particles (3.71±1.97) and Vv of vacuoles (5.72±1.58)were much larger than those (0.30±0.16 and 0.35±0.15) in the treatment group respectively (P<0.05, P<0.01). CONCLUSION: The experimental results indicate that local administration of ^32P-GMS can produce obvious effect on liver cancer cells and the anticancer effect of ^32P-GMS is directly proportional to the dose administrated. UItrastructural stereology can also show the effect of ^32P-GMS on the normalization of tumor cells, which is beneficial to the prognosis and treatment of patients. Moreover, local administrtion of ^32P-GMS is also safe.

Chromic-P32 phosphate treatment of implanted pancreatic carcinoma: Mechanism involved

AIM: To study the effects of chromic-P32 phosphate (32p colloids) interstitial administration in Pc-3 implanted pancreatic carcinoma, and investigate its anticancer mechanism.METHODS: Ninety-eight tumor bearing nude mice werekilled at different time points after the injection of 32Pcolloids to the tumor core with observed radioactivity. The light microscopy, transmission electron microscopy (TEM) and immuno-histochemistry and flow cytometry were used to study the rates of tumor cell necrosis, proliferating cell nuclear antigen index, the micro vessel density (MVD). The changes of the biological response to the lymphatic transported 32p colloids in the inguinal lymph node (ILN) were dynamically observed, and the percentage of tumor cell apoptosis, and Apo2.7, caspase-3, Bcl-2, Baxrelated gene expression were observed too.RESULTS: The half-life of effective medication is 13 dafter injection of 32P colloids to the tumor stroma, in 1-6groups, the tumor cell necrosis rates were 20%, 45%,65%, 70%, 95% and 4%, respectively (F= 4.14-105.36, P＜0.01). MVD were 38.5±4.0, 28.0±2.9, 17.0±2.9, 8.8±1.5,5.7±2.3 and 65.0±5.2 (t= 11.9-26.1, P＜0.01), respectively.Under TEM fairly differentiated Pc-3 cells were found. Thirty days after medication, tumors were shrunk and dried with scabs detached, and those in control group increased in size prominently with plenty of hypodermic blood vessels. In all animals the ILN were enlarged but in medicated animals they appeared later and smaller than those in control group. The extent of irradiative injury in ILN was positively correlated to the dosage of medication. Typical tumor cell apoptosis could be found under TEM inanimals with intra-tumoral injection of low dosed 32P colloids. The peak of apoptosis occurred in 2.96 MBq group and 24 h after irradiation. In the course of irradiationinduced apoptosis, the value of Bcl-2/Bax was down regulated; Apo2.7 and caspase-3 protein expression were prominently increased dose dependently. CONCLUSION: 32p colloids intra-tumor injection having prominent anticancer effectiveness may reveal the ability of promoting cell differentiation. The low dose 32P colloids may induce human pancreatic carcinoma Pc-3 implanted tumor cell apoptosis; Apo2.7, caspase-3, Bcl-2 and Bax protein participated in regulating the process of irradiation induced cell apoptosis.