OBJECTIVESTo study the inhibitory effect of HBx antisense oligodeoxynucleotide on the formation of transplanted hepatocellular carcinoma in nude mice.

METHOD50 nude mice were randomly divided into 5 groups: 1 control group and 4 experimental groups. Log-phase Hep3B cells endogenously expressing HBX were injected subcutaneously in nude mice. From the second day, the PAGE purified AS1, AS2, AS3 and AS4 HBx antisense oligodeoxynucleotides were injected intraperitoneally into the 4 experimental groups, respectively, on alternate days for 5 times, and distilled water was injected into the control group. Growth information of subcutaneous transplantation tumor in nude mice was recorded for 30 days. Incidence rate of transplanted tumor in different groups was compared and analyzed by survival analysis. Statistics software SPSS12.0 was used to analyze the data.

RESULTSIncidence rate of transplanted tumor was 100% in AS1, AS2, AS3 and control groups, and 90% in AS4 group (x2 = 3.995, P = 1.0). The median latency period for transplanted tumor formation was 19 days (17.48-20.52), 12 days (9.93-14.07), 11 days (9.45 to 12.55), 21 days (19.48 to 22.52), and 10 days (8.99 to 11.01) in AS1, AS2, AS3, AS4 and control group, respectively. The latency period for tumor formation was prolonged by treatment of mice with AS1 and AS4 antisense oligodeoxynucleotide (P less than 0.01).

CONCLUSIONAntisense oligodeoxynucleotide targeting to the appropriate sites of HBx gene can prolong the latency period of subcutaneously transplanted tumor in nude mice, however, the formation of transplanted tumor can not be completely blocked by limited treatment with these antisense oligos. In addition, our results suggest that peritoneal injection may be an effective way to deliver antisense oligodeoxynucleotide to living organisms.