Effect of CDK7 gene silencing against hepatoblastoma HepG2 cell proliferation

Abstract

Abstract: Objective To screen the antisense oligodeoxynucleotides (ASODN) that inhibit cultured hepatoblastoma HepG2 cell proliferation, and evaluate the antiproliferative potency of modified ASODN. Methods ASODN sequences were selected based on the secondary structure of human CDK7 mRNA predicted with RNAStructure 3.71 software. The binding thermodynamics of CDK7 mRNA to ASODN was analyzed by OligoWalk program. The sequences with the strongest effect against cultured HepG2 cell proliferation in vitro were selected, and the fragments complementary to 1-5 bases upstream or downstream to the complementary region were structurally modified and screened. Results The partial phosphorothioate ASODN complementary to 284-303 region of human CDK7 mRNA was the most powerful inhibitor, and the antiproliferative activity reached 40.4±12.6%; in the second round of screening, the antiproliferative activity of the full phosphorothioate ASODN complementary to the 287-306 region of the mRNA on HepG2 cells was 68.3±2.6%, with IC50 of 51.9±8.6 nmol/L. Conclusion Proliferation of HepG2 cells can be significantly inhibited by the screened ASODN, which might be used as a lead compound in the development of specific CDK7 inhibitors.

CLC Number:

ZHAO Ai-guo, WU Shu-guang. Effect of CDK7 gene silencing against hepatoblastoma HepG2 cell proliferation[J]. Journal of Southern Medical University, 2005, 25(01): 58-61.

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