Pak K C, Lam K Y, Law S, Tang J C O
Lo Ka Chung Centre for Natural Anti-cancer Drug Development, The Hong Kong Polytechnic University, Hong Kong SAR, P.R. China.
Int J Mol Med. 2009 Jan;23(1):121-9.
The anti-cancer effects of the anomalous fruit extract of Gleditsia sinensis (GSE) attributed to its apoptotic activity, telomerase inhibition and anti-angiogenesis in a panel of solid and non-solid tumor cell lines including esophageal squamous cell carcinoma (ESCC) have been intensively investigated by us in previous studies. Cyclooxygenase-2 (COX-2) has been well described as another promising target of cancer therapy for ESCC, and novel therapeutic agents are still being sought which target COX-2 expression. However, the anti-cancer effect of GSE through the suppression of COX-2 expression has not been previously investigated. In the present study, the anti-cancer effects of GSE on eight ESCC cell lines (KYSE 30, KYSE 150, KYSE 450, KYSE 510, KYSE 520, HKESC-3, HKESC-4 and SLMT-1) of Chinese and Japanese origins were first studied by MTS cytotoxicity assays. The effects of GSE on COX-2 expression levels and on the housekeeping form COX-1 were also investigated by multiplex RT-PCR analysis. Moreover, the anti-proliferative effect of GSE on KYSE 510 was also studied by anchorage-independent clonogenicity assay in soft agar. The results showed that GSE induced a dose- and time-dependent cytotoxicity on all of the eight ESCC cell lines and caused positive anti-proliferative action on KYSE 510 in the anchorage-independent clonogenicity assay, suggesting that GSE suppressed the in vitro growth of the ESCC cell lines. More importantly, the MRNA expression levels of COX-2, but not COX-1, in all of the ESCC cell lines were suppressed by GSE in a dose-dependent fashion. The overall results of the present study show that the anti-cancer effect of GSE on the ESCC cell lines is associated with the suppression of COX-2 expression, but not COX-1. Our findings also open a new chapter for the future advancement of GSE as a novel anti-cancer agent or as an adjuvant of traditional cancer treatments.
我们在先前的研究中已深入探究了皂荚异常果实提取物（GSE）在包括食管鳞状细胞癌（ESCC）在内的一系列实体和非实体肿瘤细胞系中的抗癌作用，这些作用归因于其凋亡活性、端粒酶抑制作用和抗血管生成作用。环氧合酶-2（COX-2）已被充分描述为ESCC癌症治疗的另一个有前景的靶点，并且仍在寻找针对COX-2表达的新型治疗药物。然而，GSE通过抑制COX-2表达产生的抗癌作用此前尚未被研究。在本研究中，首先通过MTS细胞毒性试验研究了GSE对8种源自中国和日本的ESCC细胞系（KYSE 30、KYSE 150、KYSE 450、KYSE 510、KYSE 520、HKESC-3、HKESC-4和SLMT-1）的抗癌作用。还通过多重RT-PCR分析研究了GSE对COX-2表达水平以及管家形式COX-1的影响。此外，还通过软琼脂中不依赖贴壁的克隆形成试验研究了GSE对KYSE 510的抗增殖作用。结果表明，GSE对所有8种ESCC细胞系均诱导了剂量和时间依赖性的细胞毒性，并在不依赖贴壁的克隆形成试验中对KYSE 510产生了阳性抗增殖作用，这表明GSE抑制了ESCC细胞系的体外生长。更重要的是，GSE以剂量依赖性方式抑制了所有ESCC细胞系中COX-2的mRNA表达水平，但未抑制COX-1的表达水平。本研究的总体结果表明，GSE对ESCC细胞系的抗癌作用与COX-2表达的抑制有关，而与COX-1无关。我们的发现也为GSE作为新型抗癌药物或传统癌症治疗辅助药物的未来发展开启了新篇章。
