[Study on the antisense inhibition effect of liposome-mediated radiolabled antisense oligonucleotides of c-myc mRNA].
OBJECTIVE
To ascertain whether liposome-mediated antisense oligonucleotides could inhibit the cancer cells from growing and the oncogene from expressing.


METHODS
The antisense, sense and scrambled oligonucleotides for c-myc mRNA, each containing 15 bases, were synthesized elsewhere and were labeled with 99m-technetium (99mTc-DNA). Some of them were encapsulated with liposome. Then the 99mTc-DNA and the 99mTc-DNA entrapped with liposome were transfected into colon cancer cells, LS-174-T, with different radioactivity concentrations. At different time after transfection the uptake rate of cells was measured, and the reflow rate was detected at 18 h. Inhibition effect on cellular growth was tested by MTT colorimetric experiment and on the expression of c-myc by flow cytometry.


RESULTS
The cellular uptake rate increased gradually after transfection within 5 hours, and that of liposome-mediated 99mTc-DNA was significantly higher than that of 99mTc-DNA. The reflow rate and fluorescence intensity of oncoprotein were 39.51 percent and 2.9860 +/- 0.3733 for antisense oligonucleotides, 44.12 percent and 4.2600 +/- 0.2218 for sense oligonucleotides, and 63.92 percent and 5.2620 +/- 0.8562 for mismatched oligonucleotides. The reflow rate and fluorescence intensity of liposome-entrapped 99mTc-labeled antisense oligonucleotide were significantly lower than those of sense and scrambled oligonucleotides.


CONCLUSIONS
The liposome-mediated 99mTc-labeled antisense oligonucleotides could prohibit the cancer cells from growing and the oncogene from expressing.
Zheng
Jianguo
J
Department of Nuclear Medicine, West China Hospital, Sichuan University, Chengdu 610041, China.
Tan
Tianzhi
T
Pan
Weimin
W
Zhang
Chun
C
D002455:Cell Division; D003110:Colonic Neoplasms / Q000235:genetics / Q000473:pathology*; D004247:DNA / Q000378:metabolism; D018390:Gene Targeting / Q000379:methods; D006801:Humans; D008081:Liposomes; D016376:Oligonucleotides, Antisense / Q000235:genetics*; D016271:Proto-Oncogene Proteins c-myc / Q000096:biosynthesis / Q000235:genetics*; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D013667:Technetium; D014407:Tumor Cells, Cultured
D008081:Liposomes; D016376:Oligonucleotides, Antisense; D016271:Proto-Oncogene Proteins c-myc; D012333:RNA, Messenger; D013667:Technetium; D004247:DNA