Hu Bing, An Hong-Mei, Shen Ke-Ping, Xu Ling, DU Qin, Deng Shan, Wu Yang
Department of Oncology and Institute of Traditional Chinese Medicine in Oncology;
Exp Ther Med. 2012 Jan;3(1):80-86. doi: 10.3892/etm.2011.364. Epub 2011 Oct 12.
Liver cancer ranks as the fifth most prevalent malignancy of all cancers worldwide. According to the principles of traditional Chinese medicine, liver Yin deficiency is a common clinical syndrome of liver cancer, and tonifying liver Yin is a common treatment method for liver cancer. However, no hepatocarcinoma-specific liver Yin tonifying formula has yet been established. In the present study, we established a liver cancer-specific combination of herbs, which we term liver Yin tonifying formula (LYTF). We found that LYTF inhibits the proliferation of Bel-7402 cells in a dose- and time-dependent manner. LYTF induces apoptosis in Bel-7402 cells, which is accompanied by activation of caspases-8, -9 and -3. Pan-caspase blocking completely abrogates LYTF-induced apoptosis and partially abrogates LYTF-induced proliferation inhibition. LYTF also induces cell senescence, as indicated by a large and flattened morphology, senescence-activated β-galactosidase-positive staining and G0/G1 cell cycle arrest, accompanied by the up-regulation of p16 and p21 and the down-regulation of retinoblastoma protein phosphorylation. These findings suggest that LYTF is effective in inhibiting the growth and survival of hepatocarcinoma cells through the induction of apoptosis and cell senescence. Our study also provides insight into traditional Chinese medicine methods used for the treatment of liver cancer.
肝癌是全球所有癌症中第五大最常见的恶性肿瘤。根据中医理论,肝阴虚是肝癌常见的临床证候,滋补肝阴是肝癌常见的治疗方法。然而,目前尚未建立针对肝癌的特异性滋补肝阴方剂。在本研究中,我们建立了一种针对肝癌的草药组合,称之为滋补肝阴方剂(LYTF)。我们发现LYTF以剂量和时间依赖性方式抑制Bel-7402细胞的增殖。LYTF诱导Bel-7402细胞凋亡,同时伴有半胱天冬酶-8、-9和-3的激活。泛半胱天冬酶阻断完全消除LYTF诱导的凋亡,并部分消除LYTF诱导的增殖抑制。LYTF还诱导细胞衰老,表现为细胞形态变大变扁平、衰老相关β-半乳糖苷酶阳性染色以及G0/G1期细胞周期阻滞,同时伴有p16和p21上调以及视网膜母细胞瘤蛋白磷酸化下调。这些发现表明,LYTF通过诱导凋亡和细胞衰老有效抑制肝癌细胞的生长和存活。我们的研究还为中医治疗肝癌的方法提供了见解。