Arita Y, Santiago-Schwarz F, Coppock D L
Oncology Research Laboratory, Division of Oncology, Winthrop University Hospital, Mineola, New York 11501, USA.
Melanoma Res. 2000 Oct;10(5):412-20. doi: 10.1097/00008390-200010000-00002.
Phorbol esters, which activate protein kinase C, stimulate the growth of normal human melanocytes yet inhibit the growth of most melanoma cells. We investigated whether apoptosis mediates the effects of 12-O-tetradecanoylphorbol-13-acetate (TPA) on melanocyte and melanoma cell growth. Few apoptotic cells were present when melanocytes were cultured with TPA. Upon removal of TPA, the number of apoptotic cells increased over 10 days. Addition of TPA did not induce apoptosis in a metastatic melanoma cell line, Demel, although it strongly inhibited its growth. Protection of normal melanocytes from apoptosis was associated with high levels of Bcl-2. Following withdrawal of TPA from melanocytes, the expression of Bcl-2 decreased steadily. Bax and Bcl-X(L) levels did not differ between melanoma cells or melanocytes and were unaffected by the addition of TPA. These results suggest that TPA plays an important role in stimulating the growth of melanocytes by promoting anti-apoptotic mechanisms associated with high levels of Bcl-2.
佛波酯可激活蛋白激酶C，它能刺激正常人黑素细胞的生长，但抑制大多数黑素瘤细胞的生长。我们研究了细胞凋亡是否介导12-O-十四烷酰佛波醇-13-乙酸酯（TPA）对黑素细胞和黑素瘤细胞生长的影响。当黑素细胞与TPA一起培养时，几乎没有凋亡细胞。去除TPA后，凋亡细胞数量在10天内增加。添加TPA并未在转移性黑素瘤细胞系Demel中诱导细胞凋亡，尽管它强烈抑制其生长。正常黑素细胞免受细胞凋亡与高水平的Bcl-2有关。从黑素细胞中撤去TPA后，Bcl-2的表达稳步下降。黑素瘤细胞或黑素细胞之间的Bax和Bcl-X(L)水平没有差异，并且不受TPA添加的影响。这些结果表明，TPA通过促进与高水平Bcl-2相关的抗凋亡机制，在刺激黑素细胞生长中起重要作用。
