Methods of inhibiting tumor cell proliferation
The invention provides methods for inhibiting tumor cell proliferation by inhibiting FoxM1B activity, expression, or nuclear localization in a tumor cell. The invention also provides methods for preventing tumor progression in an animal comprising inhibiting FoxM1B activity, expression, or nuclear localization. Furthermore, the invention provides methods for inhibiting tumor cell growth in an animal comprising inhibiting FoxM1B activity, expression, or nuclear localization in tumor cells in the animal.
1. A method of inhibiting proliferation of a prostate tumor cell comprising the step of inhibiting FoxM1B activity in the prostate tumor cell by contacting the cell with a p19 ARF protein fragment that can inhibit FoxM1B activity in the prostate tumor cell, wherein the p19 ARF protein fragment comprises (1) a first peptide consisting of SEQ ID NO:11, and (2) a second peptide covalently linked to the amino terminus of the first peptide, wherein the second peptide enhances cellular uptake of the p19 ARF protein fragment.
2. The method of claim 1 , wherein the second peptide is an HIV TAT peptide of SEQ ID NO:13.
3. The method of claim 1 , wherein the second peptide is a nine D-Arg peptide of SEQ ID NO:14.
4. The method of claim 1 , wherein the p19′ protein fragment comprises a fusion protein of SEQ ID NO:11 and a nine D-Arg peptide of SEQ ID NO:14.
5. The method of claim 1 , wherein the p19 ARF protein fragment consists of a fusion protein of SEQ ID NO:11 and a nine D-Arg peptide of SEQ ID NO:14.
6. The method of claim 1 , wherein the prostate tumor cell is a malignant prostate tumor cell.
7. The method of claim 1 , wherein the prostate tumor cell is of epithelial cell origin.
8. A method of inhibiting growth of a prostate tumor cell in an animal, by administering a pharmaceutical composition comprising a P19 ARF protein fragment that can inhibit FoxM1B activity in the prostate tumor cell, wherein the p19 ARF protein fragment comprises (1) a first peptide consisting of SEQ ID NO:11, and (2) a second peptide covalently linked to the amino terminus of the first peptide, wherein the second peptide enhances cellular uptake of the p19 ARF protein fragment.
9. The method of claim 8 , wherein the pharmaceutical composition further comprises at least one pharmaceutically acceptable carrier, diluent or excipient.
10. The method of claim 8 , wherein the pharmaceutical composition is administered to the animal parenterally.
11. The method of claim 8 , wherein the pharmaceutical composition is administered to the animal by intraperitoneal injection.
12. The method of claim 8 , wherein the animal is human.
13. A method of inhibiting proliferation of a prostate tumor cell comprising the step of inhibiting FoxM1B activity in the prostate tumor cell by contacting the cell with a p19 ARF protein fragment that can inhibit FoxM1B activity in the prostate tumor cell, wherein the p19 ARF protein fragment comprises (1) a first peptide from p19 ARF polypeptide and consisting of SEQ ID NO:12, and (2) a second peptide covalently linked to the amino terminus of the first peptide at p19 ARF amino acid residue position 26 of the first peptide, wherein the second peptide enhances cellular uptake of the p19 ARF protein fragment.
14. The method of claim 13 , wherein the second peptide is an HIV TAT peptide of SEQ ID NO:13.
15. The method of claim 13 , wherein the second peptide is a nine D-Arg peptide of SEQ ID NO:14.
16. The method of claim 13 , wherein the p19 ARF protein fragment comprises a fusion protein of SEQ ID NO:12 and a nine D-Arg peptide of SEQ ID NO:14.
17. The method of claim 13 , wherein the p19 ARF protein fragment consists of a fusion protein of SEQ ID NO:12 and a nine D-Arg peptide of SEQ ID NO:14.
18. The method of claim 13 , wherein the prostate tumor cell is a malignant prostate tumor cell.
19. The method of claim 13 , wherein the prostate tumor cell is of epithelial cell origin.
20. A method of inhibiting growth of a prostate tumor cell in an animal, by administering a pharmaceutical composition comprising a P19 ARF protein fragment that can inhibit FoxM1B activity in the prostate tumor cell, wherein the p19 ARF protein fragment comprises (1) a first peptide from p19 ARF polypeptide and consisting of SEQ ID NO:12, and (2) a second peptide covalently linked to the amino terminus of the first peptide at p19 ARF amino acid residue position 26 of the first peptide, wherein the second peptide enhances cellular uptake of the p19 ARF protein fragment.
21. The method of claim 20 , wherein the pharmaceutical composition further comprises at least one pharmaceutically acceptable carrier, diluent or excipient.
22. The method of claim 20 , wherein the pharmaceutical composition is administered to the animal parenterally.
23. The method of claim 20 , wherein the pharmaceutical composition is administered to the animal by intraperitoneal injection.
24. The method of claim 20 , wherein the animal is a human.