Chemoprevention of Low-Molecular-Weight Citrus Pectin (LCP) in Gastrointestinal Cancer Cells.
Chemoprevention of Low-Molecular-Weight Citrus Pectin (LCP) in Gastrointestinal Cancer Cells.
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低分子量柑橘果胶 (LCP) 对胃肠癌细胞的化学预防
DOI：
10.7150/ijbs.13988
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发表时间：
2016
影响因子：
9.2
通讯作者：
Ling ZQ
中科院分区：
文献类型：
--
作者：
Wang S;Li P;Lu SM;Ling ZQ
背景与目的：低分子量柑橘果胶(LCP)是一种富含半乳糖基(即糖类)残基的复杂多糖。在这项研究中，我们评估了LCP的抗肿瘤特性，从而导致Bclxl介导的胃肠道癌细胞凋亡的抑制。方法：以AGS胃癌和SW-480结直肠癌细胞为研究对象，观察LCP对培养细胞和肿瘤移植瘤细胞活力、细胞周期和细胞凋亡的影响。结果：LCP处理的AGS和SW-480细胞存活率显著降低(P<；0.05)。与未处理组相比，LCP处理组细胞周期相关蛋白如Cyclin B1的表达也减少。LCP治疗组的AGS或SW-480细胞系移植瘤明显小于未治疗组(P<；0.05)。LCP治疗降低了Galectin-3(GAL-3)的表达水平，而Galectin-3是导致上皮-间充质转化(EMT)逆转的肿瘤转移中的重要基因，并增加了对Bclxl和Survivin的抑制，以促进细胞凋亡。此外，结果还表明，LCP和5-FU在体内和体外对胃肠道癌细胞具有协同抑制作用。结论：LCP能有效抑制胃肠道癌细胞的生长和转移，其机制可能与下调Bclxl和Cyclin B促进细胞凋亡，抑制EMT有关。因此，LCP单独或联合其他治疗方法有很高的潜力作为一种新的治疗策略来改善胃肠癌的临床治疗。
Background & Aims: Low-molecular-weight citrus pectin (LCP) is a complex polysaccharide that displays abundant galactosyl (i.e., sugar carbohydrate) residues. In this study, we evaluated the anti-tumor properties of LCP that lead to Bcl-xL -mediated dampening of apoptosis in gastrointestinal cancer cells. Methods: We used AGS gastric cancer and SW-480 colorectal cancer cells to elucidate the effects of LCP on cell viability, cell cycle and apoptosis in cultured cells and tumor xenografts. Results: Significantly decreased cell viabilities were observed in LCP treated AGS and SW-480 cells (P<0.05). Cell cycle-related protein expression, such as Cyclin B1, was also decreased in LCP treated groups as compared to the untreated group. The AGS or SW-480 cell-line tumor xenografts were significantly smaller in the LCP treated group as compared the untreated group (P<0.05). LCP treatment decreased Galectin-3 (GAL-3) expression levels, which is an important gene in cancer metastasis that results in reversion of the epithelial-mesenchymal transition (EMT), and increased suppression of Bcl-xL and Survivin to promote apoptosis. Moreover, results demonstrated synergistic tumor suppressor activity of LCP and 5-FU against gastrointestinal cancer cells both in vivo and in vitro. Conclusions: LCP effectively inhibits the growth and metastasis of gastrointestinal cancer cells, and does so in part by down-regulating Bcl-xL and Cyclin B to promote apoptosis, and suppress EMT. Thus, LCP alone or in combination with other treatments has a high potential as a novel therapeutic strategy to improve the clinical therapy of gastrointestinal cancer.