Connexin enhances chemotherapy-induced apoptosis in human cancer cells inhibiting tumor cell proliferation

摘要

The present invention provides methods and compositions for the inhibition of proliferation rate of target cells, for example tumor cells. In particular, a nucleic acid encoding a connexin protein, fragment, derivative or analog thereof can be incorporated into a target cell. Expression of the nucleic acid sequence encoding the connexin protein, fragment, derivative or analog thereof, particularly connexin 43 and non-phosphorylated connexin 43, reduces the level of bcl-2 expression in the cells thereby inducing the cells to enter apoptosis. Connexin protein, fragments, derivatives, or analogs thereof can also be administered to the cell population to reduce bcl-2 expression inducing apoptosis in the cell population. It has further been found that the addition of an antagonist of MCP-1 activity can enhance the effects of connexin on tumor cell proliferation. Also, the prognosis of a subject undergoing standard chemotherapy can be assessed by correlating the expression levels of connexin and bcl-2.