Hu Bing, Du Qin, Deng Shan, An Hong-Mei, Pan Chuan-Fang, Shen Ke-Ping, Xu Ling, Wei Meng-Meng, Wang Shuang-Shuang
Department of Oncology, Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai 202032, P.R. China.
Department of Science and Technology, Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai 200032, P.R. China.
Oncol Rep. 2014 Sep;32(3):1037-42. doi: 10.3892/or.2014.3312. Epub 2014 Jul 7.
Nü-zhen-zi, the fruit of Ligustrum lucidum Ait., is one of the most frequently used liver Yin tonifying Chinese herbs for the treatment of liver cancer. However, the effect of Ligustrum lucidum fruit on hepatocarcinoma cells remains unknown. In the present study, we evaluated the effects of a Ligustrum lucidum fruit extract (LLFE) on human hepatocellular carcinoma Bel-7402 cells. The results showed that LLFE inhibited the proliferation of the Bel-7402 cells in a dose- and time-dependent manner. LLFE induced apoptosis in Bel-7402 cells accompanied by activation of caspase-3, -8 and -9. LLFE-induced apoptosis was completely abrogated by a pan caspase inhibitor, Z-VAD-FMK. LLFE treatment also caused a large and flat morphologic cellular change, positive SA-β-gal staining, and G0/G1 phase cell cycle arrest in the Bel-7402 cells, accompanied by upregulation of p21 and downregulation of RB phosphorylation. Specific knockdown of p21 expression by RNA interference partially abrogated LLFE-induced apoptosis, and significantly abrogated LLFE-induced cell senescence. These observations suggest that Nü-zhen-zi is a potential anticancer herb and support the traditional use of Nü-zhen-zi for hepatocarcinoma treatment.
女贞子，为木犀科植物女贞的果实，是治疗肝癌最常用的滋补肝阴的中药之一。然而，女贞子果实对肝癌细胞的作用尚不清楚。在本研究中，我们评估了女贞子果实提取物（LLFE）对人肝癌Bel-7402细胞的影响。结果表明，LLFE以剂量和时间依赖性方式抑制Bel-7402细胞的增殖。LLFE诱导Bel-7402细胞凋亡，同时伴有caspase-3、-8和-9的激活。泛半胱天冬酶抑制剂Z-VAD-FMK完全消除了LLFE诱导的凋亡。LLFE处理还导致Bel-7402细胞出现大而扁平的形态学细胞变化、SA-β-半乳糖苷酶染色阳性以及G0/G1期细胞周期阻滞，同时伴有p21上调和RB磷酸化下调。通过RNA干扰特异性敲低p21表达可部分消除LLFE诱导的凋亡，并显著消除LLFE诱导的细胞衰老。这些观察结果表明，女贞子是一种潜在的抗癌草药，并支持女贞子在肝癌治疗中的传统应用。
