Paclitaxel Induces Apoptosis in AIDS-Related Kaposi's Sarcoma Cells

[摘要] Paclitaxel is a microtubule stabilizing drug that causes dividing cells to arrest and then undergo apoptosis. It also has antiangiogenicactivity because it alters cytoskeletal structure, affecting migration and invasion. Paclitaxel is an effectivetreatment for AIDS-related Kaposi’s sarcoma (KS). KS is a tumor in which there is marked proliferation of endothelial cellsin addition to the tumor cells, which themselves share many markers with activated (proliferating) endothelial cells.Wesought to determine the mechanism by which paclitaxel exerts its anti-KS tumor effects.In vitro, KS cells are very sensitiveto paclitaxel, with half-maximal growth inhibition observed at 0.8 nM. Inhibition of migration of KS cells was also observedat nanomolar concentrations of the drug. Paclitaxel induced cell cycle arrest with an accumulation of cells in sub-G1.Thiswas accompaniedin vitroby various events typical of apoptosis: phosphorylation of two anti-apoptotic proteins Bcl-2 andBcl-xL, release of cytochrome c into the cytoplasm, cleavage and activation of caspase-3.In vitroresults were borne out bystudies of KS tumor xenografts in nude mice. Paclitaxel (10 mg/kg) inhibited tumor growth by 75% over 21 days.Histological examination of the tumors revealed a decrease in proliferative index, a decrease in the number of mitotic figuresand an increase in apoptotic cells compared to tumors from untreated mice.

[学科分类] 肿瘤学