Study On The Effect Of HTR-antisense Oligodeoxynucleotide In Combination With DDp On The Human Gastric Carcinoma Transplanted Subcutaneously In Nude Mice In Vivo

Objective: Telomeres, specialized heterochromatic structures at the ends of vertebrate chromosomes, are implicated in stabilizing and protecting chromosomes, anchoring chromosomes, and assisting in the replication of linear DNA. Telomerase is a unique ribonucleoprotein that can synthesize telomeric DNA onto chromosomal ends using a segment of its RNA component (hTR) as a template to compensate for the lose of telomeric repeats (TTAGGG) caused by the so-called "end-replication" problem, and telomerase plays an important role in carcinogenesis. It is telomerase inhibition that may serve as an effective new tool for eliminating tumor cells. To study the whether hTR antisense PS-ODN has anticancer effect and the effect of increasing the susceptibility of tumor to DDP, we explore the effect of hTR-antisense oligodeoxynucleotide in combination with DDP on the human gastric carcinoma transplanted subcutaneously in nude mice in vivo.Methods: The model of human gastric carcinoma transplanted subcutaneously was established in thirty nude mice, then divided randomly into 5 groups (Control group, ASODN group, RODN group, DDP group and ASODN+DDP group). The weight of nude mice was measured, and the tumor growth inhibitory rate was calculated, too. The relative telomerase activity was quantitatively measured by TRAP PCR-ELISA methods. Results: The maximum of the tumor inhibitory rate in ASODN+DDP group,ASODN group, DDP group and RODN group was 94. 2%, 84. 3%, 92. 8% and 26. 9%respectively. There was significantly different in the relativetelomerase activity among four treatment groups.Conclusions: The results suggested that hTR antisense PS-ODN may actas a specific tumor growth inhibitor and telomerase activity inhibitormay be in sequence specific manner, and have the effect of increasingthe susceptibility of transplanted tumor to DDP.