Expression of cyclin-dependent kinase inhibitor genes induces apoptosis in human hepatoma cell line

Abstract

APOPTOSIS is an active, inherently programmed cell death, which has typical morphological and biochemical characteristics. Cell death during embryonic development, shaping of the T and B lymphocyte and tissue dystrophy related to endocrine is designated a physiological apoptosis by which cell numbers can be effectively controlled. As a process opposite to cell division, there is a balance between apoptosis and cell proliferation. A tumor will develop once the balance is disturbed and the cell division is more rapid than the cell death. Also, apoptosis is under the control of multiple molecular components, while cell division is under the control of the cell cycle engine. The precise control of cell proliferation and differentiation is essential for the proper development of a multicellular organism. A series of regulatory genes consist of a complex network to control when the cells divide and differentiate. The currently increasing evidence has indicated that the cyclin dependent kinase (CDKs) played a key role in this network of cell cycle regulatory machinery. These kinases are positively regulated by cyclin molecules and are essential for cell cycle progression[11, while CDK inhibitors (CKIs) can specifically[21 bind and inhibit CDK activities. CDK inhibitors consist of two classes. One is the dual-specificity family, comprising p21, p27 and p57 which can bind nearly all GI phase cyclin/CDK complexes and arrest cell cycles at GI phase. The other is the ankyrin family, including p15, p16, p18 and p19 which can inhibit CDK4 and CDK6 selectively and arrest cell cycles on GI phase or give them entry into Go phase[31. Cells after DNA damage will be arrested at G1 phase and repaired or undergo apoptosis in some pathways. So it has been a potential strategy using CKI genes to induce apoptosis in carcinoma cells. In this study, we delivered CKI genes (p15, p16, p21) into human hepatoma cells by non-viral receptor-mediated vector. The results showed that the growth of transfected hepatoma cells was inhibited and there exists apoptosis induced by the expression of CKI genes.