Bioresource Sciences, Andong National University, Andong 760749, Republic of Korea.
Biochem Biophys Res Commun. 2010 Oct 1;400(4):752-7. doi: 10.1016/j.bbrc.2010.08.142. Epub 2010 Sep 15.
Benzo[a]pyrene (BaP) is an environment carcinogen that can enhance cell proliferation by disturbing the signal transduction pathways in cell cycle regulation. In this study, the effects of 2M4VP on cell proliferation, cell cycle and cell cycle regulatory proteins were studied in BaP-treated NIH 3T3 cells to establish the molecular mechanisms of 2M4VP as anti-proliferative agents. 2M4VP exerted a dose-dependent inhibitory effect on cell growth correlated with a G1 arrest. Analysis of G1 cell cycle regulators expression revealed 2M4VP increased expression of CDK inhibitor, p21Waf1/Cip1 and p15 INK4b, decreased expression of cyclin D1 and cyclin E, and inhibited kinase activities of CDK4 and CDK2. However, 2M4VP did not affect the expression of CDK4 and CDK2. Also, 2M4VP inhibited the hyper-phosphorylation of Rb induced by BaP. Our results suggest that 2M4VP induce growth arrest of BaP-treated NIH 3T3 cells by blocking the hyper-phosphorylation of Rb via regulating the expression of cell cycle-related proteins.
苯并[a]芘（BaP）是一种环境致癌物，可通过干扰细胞周期调控中的信号转导途径来增强细胞增殖。在这项研究中，研究了 2M4VP 在 BaP 处理的 NIH 3T3 细胞中对细胞增殖、细胞周期和细胞周期调节蛋白的影响，以建立 2M4VP 作为抗增殖剂的分子机制。2M4VP 对细胞生长表现出剂量依赖性抑制作用，与 G1 期阻滞相关。对 G1 细胞周期调节剂表达的分析表明，2M4VP 增加了 CDK 抑制剂 p21Waf1/Cip1 和 p15 INK4b 的表达，降低了 cyclin D1 和 cyclin E 的表达，并抑制了 CDK4 和 CDK2 的激酶活性。然而，2M4VP 并不影响 CDK4 和 CDK2 的表达。此外，2M4VP 抑制了 BaP 诱导的 Rb 过度磷酸化。我们的结果表明，2M4VP 通过调节细胞周期相关蛋白的表达，阻断 Rb 的过度磷酸化，诱导 BaP 处理的 NIH 3T3 细胞生长停滞。
