ABSTRACT
Tubulin has been shown to be an effective target for the development of cytotoxic agents against prostate cancer. Previously, we reported that Lx2-32c is an anti-tubulin agent with high binding affinity to tubulin. In this study, we investigated the potential of Lx2-32c to act as an effective cytotoxic agent in the treatment of prostate cancer. MTT assays showed that Lx2-32c was cytotoxic to all tested prostate cancer cell lines. The Lx2-32c-treated cells typically exhibited a rounded morphology associated with the onset of apoptosis, as evidenced by immunocytochemical staining. Human prostate cancer cell lines treated with Lx2-32c arrest in the G2/M phase of the cell cycle and the treatment is associated with an increased ratio of cells in the sub-G0/G1 phase as determined by flow cytometry. Furthermore, expression of the cleaved form of poly (ADP-ribose) polymerase in prostate cancer cell lines treated with Lx2-32c was shown by Western blotting assay. Xenograft implants of LNCaP and PC3-derived tumors in nude mice showed that Lx2-32c treatment significant inhibited tumor growth with effects equivalent to those of docetaxel. These findings demonstrate the potential of Lx2-32c as a candidate antitumor agent for the treatment of prostate cancer.
ABSTRACT
Objective To make clear of the mechanism of metastasis and recurrence of primary liver cancer, and to make sure of the preventive value of transeatheter arterial immun- ehemoembolization (ICE) in treatment of liver cancer. Methods The study is a double-blinded, controlled, prospective, randomized trial. 146 patients were randomly divided into 3 groups. Group A: regular surgery of primary liver cancer;group B: TACE 1month after surgery, treatment proposal was: ADM + DDP + 5-Fu + LP; group C:transeatheter arterial immun-chemoembolization 1 month after surgery, treatment proposal : ADM + DDP +5-Fu+LP+Octreotide+IFN. Results CD3+, CD4+, CD4+/CD8+ increased 1 month after surgery in group A; In group B: CD3+, CD4+, CD4+/CD8+ decreased but CD8+ increased 1 week after TACE; CD3+, CD4+, CD4+ /CD8+ increased but CD8+ decreased 4 weeks after TACE(P<0.05); In group C: CD3+ , CD4+, CD4+/CD8+ increased slightly 1 week after TACE, but increased significantly 4 weeks later(P<0.05). In group A, the level of VEGF was high before surgery but decreased 1 month after surgery; In group B, the level of VEGF decreased 1 week after TACE, decreased more significantly 4 weeks after TACE than that in group B(P <0.05). 1 year survival rate, 2 year survival rate and 3 year survival rate in group C ware higher than those in group A; 1 year survival rate was higher in group B than that in group A, however, 2 year survival had and 3 year survival rate had no differ-ences between group B and group A. Conclusion Transcatheter arterial ICE can prevent metastasis and recurrence after surgery of primary liver cancer increase the 1,2,3 year survival rate. It not only has the role of TACE,but can increase the immunefunction,and inhibit tumor angiogenesis, then increase the therapeutic effect.