ABSTRACT: ObjectiveTo observe the effects of sense and antisense oligodeoxynucleotides of tankyrase 1 (TANK1-SODN and TANK1-ASODN) on murine
tumor growth following intratumoral injection, investigate the actual suppressing result and mechanism of TANK1-ASODN on cancer
cell proliferation, and discuss the possibility of using it in gene therapy on human lung cancer cells.
MethodsAft er BALB/c nude mice had been subcutaneously inoculated with human lung cancer cell line CALU and it had grown into tumor
nodules, we distributed these mice randomly into 3 groups: 4 in saline treatment group, and 5 each in TANK1-SODN group, and
TANK1-ASODN groups. Then multiple direct intratumoral injections of synthesized TANK1-ASODN given continuously into tumor
nodules for 16 days, this was compared with TANK1-SODN and saline control groups. During the experiment we measured the tumor
volume every 5 days with vernier calipers; observed the histopathological characteristics of tumor tissues under microscope;
went further to detect the minute changing of ultrastructure of cancer cells by electron microscope; tested the expression
levels of ki67 and hTERT protein by means of SABC immunohistochemical method; and detected the lung cancer cells’ hTERT mRNA
expression level by hybridization in situ (ISH) in each group.
ResultsAfter 16 days of continuous injection, the tumor volume in TANK1-ASODN group was significantly smaller than the other 2 groups
(both P < 0.01); quite a lot of tumor cell degeneration and necrosis were observed in mice given TANK1-ASODN. The results of electron
microscope also showed that TANK1-ASODN has the power to kill cancer cells in various ways. Moreover, statistically significant
decreases in the positive expression ratio of Ki67 Labeling Index (P < 0.01), hTERT protein (P < 0.01), and hTERT mRNA (P < 0.01) were consistently observed in the TANK1-ASODN group.
ConclusionHuman lung cancer cell line CALU expressed high telomerase activity. TANK1-ASODN had the ability to decline the high expression
level of hTERT; inhibit the activity of telomerase, accelerate tumor cell degeneration and necrosis; and then suppress the
proliferation of cancer cells.
Key WordsTANK1-ASOND-intratumoral injection-CALU-gene therapy
Clinical Oncology and Cancer Research 04/2012; 7(3):181-186.