| ObjectiveTo study one of non - steroidal anti - inflammatory drugs ( NSAIDs) - -indomethacin (IN) 's growth - inhibition mechanism towards rats'Lewis pulmonary tumor, to supply theoretical evidence for the anti - tumor use of IN in clinical.MaterialsOne Lewis pulmonary tumor model rat, 45 C57BL/6 inbred strain rats (6 ~8weeks, weighed 20 ±2g,male, ordinary).~3H -indomethacin (~3H - IN: radiochemical purity >90%;specific activity > 180GBq/g) was labed by tritium - labled laboratory of isotope institute of china atomic energy scientific academy. Bel -2 and Bax polyclonal antibody, SP immunohistochemistry kit and DAB coloration liquid. H - 600 transmission electron microscope.Methods45 C57BL/6 inbred strain rats were made into Lewis pulmonary tumor model rats. 20 rats were taken out randomly when the longest diameter of their tumors was about 5mm, and were divided into 2 groups. Rats in treatment group were given IN (3mg/kg) once a day, in control group given the same volum saline. The long and short diameter were measured by sliding caliper to calculatetumor volums before given IN every day. Rats were killed after given IN 20 days. The anti - tumor rate of IN was calculated through volumetric method, the expression of anti - apoptosis protein Bel - 2 and support - apoptosis protein Bax were detected by immunohistochemistry.The other 25 bearing tumor rats were divided into 5 groups. When the longest diameter of their tumors was about 1. 0cm ~ 1. 5 cm. Every rat was given 180 kBq (0.2 mL) 3H - IN (including 3H - IN 90 |xg). Then all rats were killed to take out tumor tissues after given H - IN 4hN7hx12h%24hx36h . Micro autoradiography technique was used to observe the subcellular localization of IN in Lewis pulmonary tumor.ResultsThe weight of tumor in treatment group and control group is 3. 28 ±1. 17g and 7. 28 ±2. lOg seperately when experiment is over, they have significant differences (t =3.355 ,P <0.01.). The volum of tumor is 3.25 ± 1.05 cm and 7. 23 ±2. 03 cm3,they have significant differences (t = 5. 527, P < 0. 001) too. Tumor growth can be inhibited obviously by IN in treatment group, inhibition rate of IN is 55.05%.Immunohistochemistry results show that Integrated Optical Density Total (IODT) of Bel -2 is 73817 ± 8079 and 100156 ± 10859 seperately in treatment group and control group, the expression of Bel - 2 protein can be dramatically decreased by IN (t = 6. 154, P < 0. 001). IODT of Bax is 82857 ± 13342 and 85316 ± 13654, no obviously influence is found on Bax expression (t =2. 101, P > 0. 05). So IN can degrade the ratio of Bel - 2/Bax.Autoradiography results show that the black silver granules of H - IN distribute in cellullar membrane, plasm and nucleaus of Lewis pulmonary tumor after given IN 4%7X12X24 and 36 h. The average quantities of silver granules at 12h are higher than at 4,7,24 and 36 h.ConclusionsIN can inhibit the growth of Lewis pulmonary tumor and induce its apopto-sis. IN ' s anti - tumor mechanism may be in association with its down - regulating the expression of Bel - 2 protein and reduction the ratio of Bel - 2/Bax. IN distributes in cellullar membrane, plasm and nucleaus of Lewis pulmonary tumor.
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