Identification of modulators of serine protease inhibitor kazal and their use as anti-cancer and anti-viral agents

An siRNA which is a member selected from the group consisting of L71 siRNA comprising sense and anti-sense oligonucleoside with the SPIK sequence of SEQ ID NO:

• 1, as shown in FIGS. 9, and L183 comprising sense and anti-sense oligonucleoside with the SPIK sequence SEQ ID NO:
• 2, as shown in FIG. 9.

A diagnostic kit comprising an antibody to SEQ ID NO:4 or SEQ ID NO:5 to diagnose patients exhibiting hepatitis C virus infection symptoms or at risk for developing a disease, wherein the disease is hepatitis B virus infection, hepatitis C virus infection, hepatitis, cancer, or hepatic cancer.

An inhibitor of SPIK expression or function used for treatment of a disease which is hepatitis B virus infection, hepatitis C virus infection, hepatitis, cancer, or hepatic cancer.

A method of identifying therapeutically effective compounds comprising determining the ability of test agents to modulate SPIK serine protease inhibitory activity in apoptosis sensitive cells expressing SPIK exposed to apoptotic agents, wherein the test agent is a compound determined to have potential therapeutic efficacy if the apoptosis of the cells in response to the agents changes compared to control cells not exposed to the test agent.

A method for identifying a compound which is an inhibitor of SPIK expression comprising:

• (a) contacting a test agent in vitro with a cell that expresses SPIK protein;
• (b) determining the expression level of the SPIK protein in the cell;
• and (c) determining whether the expression level determined in step (b) is lower than the SPIK protein expression level determined in the absence of the test agent, such lower expression level indicating that the compound is an inhibitor of SPIK expression.

A method of screening for a compound that inhibits, diminishes, or modulates anti-apoptotic activity in an eukaryotic cell, said method comprising:

• (a) introducing into eukaryotic cells an expression vector comprising a polynucleotide encoding a SPIK polypeptide, or fragment thereof, having serine protease inhibitory activity, (b) treating one fraction of said cells with a test agent and leaving a second fraction of said cells untreated as a control, (c) treating both fractions of cells with an agent that induces cell death, and (d) detecting an inhibition, diminution or modulation in anti-apoptotic activity in the fraction of cells treated with the test agent in comparison to the untreated control, thereby screening for a test agent which is a compound that inhibits, diminishes, or modulates anti-apoptotic activity in an eukaryotic cell.