Tang Wing K, Chui Chung H, Fatima Sarwat, Kok Stanton H L, Pak Kai C, Ou Tian M, Hui Kin S, Wong Mei M, Wong John, Law Simon, Tsao S W, Lam King Y, Beh Philip S L, Srivastava Gopesh, Ho Kwok P, Chan Albert S C, Tang Johnny C O
Department of Applied Biology and Chemical Technology, The Hong Kong Polytechnic University, Hong Kong, P.R. China.
Int J Mol Med. 2007 Jun;19(6):953-60.
Previous studies have shown that the anomalous fruit extract of Gleditsia sinensis (GSE) exhibited apoptotic properties in various solid and non-solid tumors in vitro. However, the inhibitory actions of GSE on oncogenic expression and telomerase activity in esophageal squamous cell carcinoma (ESCC) have not been studied before. In the present study, the anti-cancer effects of GSE were demonstrated in three ESCC cell lines (HKESC-1, HKESC-2 and SLMT-1) by MTS and anchorage-independent clongen-icity assays, expression studies on oncogenes at 11q13 (CCND1, INT2, FGF4 and EMS1) and real-time quantitative telomeric repeat amplification protocol assay to show the inhibitory effect of GSE on telomerase in ESCC. The means of MTS50 of GSE for the ESCC cell lines and non-tumor NIH 3T3 cells were 21 and 163 microg/ml respectively. The anchorage-independent clongenicity assay showed that SLMT-1 cells lost their colony-forming potential which was dose-dependent to GSE. Moreover, GSE demonstrated dose-dependent suppression on the expression of INT2, EMS1 and FGF4, and inhibition of telomerase activity in the ESCC cell lines. Our overall results thus provide the first evidence that the anti-cancer effects of GSE on ESCC involve the suppression of oncogenic expression and inhibition of telomerase activity. Our findings also offer a new opportunity for the future development of GSE as a novel anti-cancer agent for ESCC and possibly for other cancers.
先前的研究表明，皂荚异常果实提取物（GSE）在体外对各种实体瘤和非实体瘤均表现出凋亡特性。然而，GSE对食管鳞状细胞癌（ESCC）致癌基因表达和端粒酶活性的抑制作用此前尚未被研究。在本研究中，通过MTS和非锚定依赖性克隆形成试验、对11q13处致癌基因（CCND1、INT2、FGF4和EMS1）的表达研究以及实时定量端粒重复序列扩增协议试验，在三种ESCC细胞系（HKESC-1、HKESC-2和SLMT-1）中证明了GSE的抗癌作用，以显示GSE对ESCC中端粒酶的抑制作用。GSE对ESCC细胞系和非肿瘤NIH 3T3细胞的MTS50平均值分别为21和163μg/ml。非锚定依赖性克隆形成试验表明，SLMT-1细胞失去了其集落形成潜力，这与GSE呈剂量依赖性。此外，GSE对ESCC细胞系中INT2、EMS1和FGF4的表达表现出剂量依赖性抑制，并抑制端粒酶活性。因此，我们的总体结果首次证明了GSE对ESCC的抗癌作用涉及抑制致癌基因表达和抑制端粒酶活性。我们的研究结果也为GSE作为一种新型的ESCC抗癌药物以及可能对其他癌症的未来开发提供了新的机会。
