Chung Kwang-Hoe, Kim Sung-Hoon, Han Kyu-Yeon, Sohn Young-Doug, Chang Soo-Ik, Baek Kwang-Hyun, Jang Yangsoo, Kim Doo-Sik, Kang In-Cheol
Cardiovascular Research Institute and BK21 Project for Medical Sciences, Yonsei University College of Medicine, Seoul 120-752, Korea.
J Pharm Pharmacol. 2003 Nov;55(11):1577-82. doi: 10.1211/0022357022160.
We have investigated the inhibitory effect of salmosin on integrin-mediated human tumour cell proliferation. SK-Mel-2 human melanoma cell adhesion to denatured collagen or vitronectin was found to be significantly and statistically inhibited by salmosin in a dose-dependent manner (P<0.05). Moreover, the binding of SK-Mel-2 cells to salmosin-coated plates was specifically disrupted by anti-integrin alphav monoclonal antibody at 8 microg mL(-1), but not by anti-integrin monoclonal antibody. These findings indicated that salmosin inhibited the adhesion of SK-Mel-2 cells to denatured collagen by specifically blocking integrin alphav. The proliferation of SK-Mel-2 cells on a denatured collagen-coated plate was statistically and significantly inhibited by salmosin induced apoptosis in a dose-dependent manner (P<0.05). Anti-integrin alphav monoclonal antibody, anti-integrin alphavbeta3 monoclonal antibody, and synthetic RGD peptide also suppressed SK-Mel-2 cell proliferation. Several lines of experimental evidence strongly suggested that the inhibition of SK-Mel-2 cell proliferation by salmosin was due to the induction of apoptosis via the blocking of integrin alphav-mediated cell survival.
我们研究了鲑精蛋白对整合素介导的人肿瘤细胞增殖的抑制作用。发现鲑精蛋白能以剂量依赖的方式显著且在统计学上抑制SK-Mel-2人黑色素瘤细胞与变性胶原蛋白或玻连蛋白的黏附（P<0.05）。此外，8μg/mL的抗整合素αv单克隆抗体能特异性破坏SK-Mel-2细胞与包被有鲑精蛋白的平板的结合，但抗整合素单克隆抗体则不能。这些发现表明，鲑精蛋白通过特异性阻断整合素αv来抑制SK-Mel-2细胞与变性胶原蛋白的黏附。鲑精蛋白能以剂量依赖的方式诱导凋亡，从而在统计学上显著抑制SK-Mel-2细胞在变性胶原蛋白包被平板上的增殖（P<0.05）。抗整合素αv单克隆抗体、抗整合素αvβ3单克隆抗体和合成RGD肽也能抑制SK-Mel-2细胞增殖。多条实验证据有力地表明，鲑精蛋白对SK-Mel-2细胞增殖的抑制作用是由于通过阻断整合素αv介导的细胞存活来诱导凋亡。
