ABSTRACT
Lung cancer is one of the malignant tumors with high incidence rate and high mortality worldwide. Telomere and telomerase are closely related to the occurrence and development of lung cancer. Although telomerase may not be the direct cause of carcinogenesis, it plays a key role in maintaining telomere length and tumor growth. The length of most tumors, including lung cancer, is shortened. The change of telomere length is related to the risk of lung cancer, and may become the therapeutic target and predictive index. Target drugs for telomere and telomerase signaling pathway are constantly being explored, and drugs represented by telomerase inhibitors are expected to be used in clinical treatment of lung cancer in the future. However, the research on telomere and telomerase is far from enough. The bypass mechanism of telomere length maintenance may be the direction of further research. .
ABSTRACT
OBJECTIVE:To study the inhibitory effects of recombinant adenovirus Ad-GFP-C197, which prepared by adenovirus vector system-loading human telomerase reverse transcriptase(hTERT)C fragment(C197),on the proliferation of 3 kinds of tumor cells in vitro. METHODS:Ad-GFP-C197 was amplified and purified with HEK293 cells. Human gastric cancer cells SGC7901,human breast cancer cells MCF7 and human colorectal cancer cells CaCO2 were infected by Ad-GFP-C197 respectively. Using blank adenovirus carrier (Ad-GFP) as reference,the protein expression of C197 in 3 kinds of tumor cells infected by Ad-GFP-C197 was detected by Western blot assay. The inhibitory effects of Ad-GFP-C197 on 3 kinds of tumor cells were detected by MTT assay. The cell proliferation curve was drawn and the proliferation inhibition rate was calculated. RESULTS:The protein expression of C197 was not detected in 3 kinds of tumor cells infected by Ad-GFP,while significant protein expression of C197 was found in above cells infected by Ad-GFP-C197. The proliferation curves of the 3 kinds of tumor cells infected by Ad-GFP-C197 were significantly inhibited with the time extended,and the proliferation inhibitory rate reached 37.31%-41.42%. CONCLUSIONS:Ad-GFP-C197 shows significant inhibitory effects on the proliferation of SGC7901,MCF7 and CaCO2 cells, which is rapid to make up for the slow effect of other telomerase inhibitors.
ABSTRACT
Telomerase can inhibit the shortening of telomere and stimulate continuous cell proliferation to form tumor.The activity of telomerase can be prohibited by G-quadruplex formed by the single chain in G-rich field of telomere 3' end, resulting in tumor cell apoptosis.Ligands which can induce the formation or stabilize the structure of G-quadruplex in G-rich field of oncogene exhibit antitumor function. Nowadays it becomes the core concern of chemists and biologists to screen and structurally design the compounds targeting G-quadruplex.This paper summarized the discoveries in the G-quadruplex-targeted telomerase inhibitors in recent years.