Knockdown of LMP1-induced miR-155 sensitizes nasopharyngeal carcinoma cells to radiotherapy in vitro.

The present study aimed to confirm the promotion of microRNA (miR)-155 expression by latent membrane protein 1 (LMP1), and to recognize the oncogenic role of LMP1 and LMP1-promoted miR-155 in nasopharyngeal carcinoma (NPC), particularly the influence of miR-155 knockdown on the radiosensitivity of CNE-2 cells. Following the regulation of the levels of LMP1 or miR-155 and/or subsequent to radiation treatment, the proliferation ability of CNE-2 cells was examined using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide, colony formation and Cell Counting Kit-8 assays. The results demonstrated that miR-155 was upregulated by overexpression of LMP1 in CNE-2 cells, and LMP1 overexpression and miR-155 mimic transfection increased CNE-2 cell proliferation, whereas miR-155 knockdown attenuated the promotion of CNE-2 cell growth induced by LMP1 overexpression. Furthermore, knockdown of miR-155 enhanced the radiosensitivity of CNE-2 cells. In conclusion, the present study confirmed the oncogenic role of miR-155 in NPC, and demonstrated that knockdown of miR-155 inhibited the growth of NPC cells and sensitized NPC cells to radiotherapy.

Effect of analogs with modified prenyl side chains on growth of serum deficient HL60 cells.

This study was organized by Professor Karl Folkers with the objective of finding derivatives of coenzyme Q which could be more effectively absorbed and would give better biomedical effects. In this series all the compounds are 2,3 dimethoxy, 5 methyl p benzoquinone with modified side chains in the 6 position. The modifications are primarily changes in chain length, unsaturation, methyl groups and addition of terminal phenyl groups. The test system evaluates the growth of serum deficient HL60, 3T3 and HeLa cells in the presence of coenzyme Q10 or coenzyme Q analogs. Short chain coenzyme Q homologues such as coenzyme Q2 give poor growth but compounds with saturated short aliphatic side chains from C10 to C18 produce good growth. Introduction of a single double bond at the 2' or 8' position in the aliphatic chain retains growth stimulation at low concentration but introduces inhibition at higher concentration. Introduction of a 3' methyl group in addition to the 2' enyl site in the side chain decreases the growth response and maintains inhibition. Addition of a terminal phenyl group to the side chain from C5 to C10 can produce analogs which give strong stimulation or strong inhibition of growth. The action of the analogs is in addition to the natural coenzyme Q in the cell and is not based on restoration of activity after depletion of normal coenzyme Q. The effects may be based on any of the sites in the cell where coenzyme Q functions. For example, coenzyme Q2 is known to decrease mitochondrial membrane potential whereas the analog with a 10C aliphatic side chain increases potential. Both of these compounds stimulate plasma membrane electron transport. Inhibition of apoptosis by coenzyme Q may also increase net cell proliferation and the 10C analog inhibits the permeability transition pore.

Cytokine inhibition of transplasma membrane election transport.

Two cytokines, interferon gamma and tumor necrosis factor alpha, which can inhibit cell proliferation or induce cell death, have been found to inhibit transplasma membrane electron transport. The concentrations required for inhibition of election transport are similar to concentrations effective in inhibition of cell growth. Since inhibition of election transport has been related to apoptosis and modification of election transport can cause oxygen radical formation, the changes in electron transport induced by the cytokines can contribute to known mechanisms of cytokine cytotoxicity.