Liang Xiaohui, Wang Ping, Yang Chun, Huang Fei, Wu Hui, Shi Hailian, Wu Xiaojun
Shanghai Key Laboratory of Compound Chinese Medicines, The Ministry of Education (MOE) Key Laboratory for Standardization of Chinese Medicines, The SATCM Key Laboratory for New Resources and Quality Evaluation of Chinese Medicines, Institute of Chinese Materia Medica, Shanghai University of Traditional Chinese Medicine, Shanghai, China.
Front Pharmacol. 2021 Apr 26;12:646628. doi: 10.3389/fphar.2021.646628. eCollection 2021.
Galangin, a flavonoid isolated from the rhizome of (Hance), exerts anticancer activities against many cancer cells such as liver cancer, breast cancer, lung cancer and esophageal cancer. However, the effect, as well as the underlying molecular mechanism of galangin on gastric cancer remains to be elucidated. In the present study, galangin inhibited cell viability of MGC 803 cells but not normal gastric mucosal epithelial GES-1 cells. It suppressed cell proliferation accompanied by reduced Ki67 and PCNA expression, promoted apoptosis shown by decreased Bcl-2 and elevated cleaved caspase-3 and cleaved PARP. And, galangin significantly inactivated JAK2/STAT3 pathway. When STAT3 was overexpressed, the proliferation inhibition and apoptosis promotion induced by galangin were abrogated. Meanwhile, galangin increased ROS accumulation, and reduced Nrf2 and NQO-1, but elevated HO-1 in MGC 803 cells. NAC, a ROS scavenger, rescued ROS over-accumulation and proliferation inhibition of galangin. STAT3 overexpression also counteracted excessive ROS accumulation induced by galangin. Consistent with the experiments, in nude mice exnografted with MGC 803 cells, galangin inhibited tumor growth and reversed the abnormally expressed proteins, such as p-JAK2, p-STAT3, Bcl-2, cleaved caspase-3, cleaved PARP, and Ki67. Taken together, galangin was suggested to inhibit the growth of MGC 803 cells through inducing apoptosis and decreasing cell proliferation, which might be mediated by modulating STAT3/ROS axis. Our findings implicate a potential application of galangin for gastric cancer therapy possibly with low toxicity.
高良姜素是从山奈（Hance）根茎中分离出的一种黄酮类化合物，对许多癌细胞如肝癌、乳腺癌、肺癌和食管癌具有抗癌活性。然而，高良姜素对胃癌的作用及其潜在分子机制仍有待阐明。在本研究中，高良姜素抑制MGC 803细胞的细胞活力，但对正常胃黏膜上皮GES-1细胞无抑制作用。它抑制细胞增殖，同时Ki67和PCNA表达降低；促进细胞凋亡，表现为Bcl-2表达降低，裂解的caspase-3和裂解的PARP表达升高。此外，高良姜素显著使JAK2/STAT3信号通路失活。当STAT3过表达时，高良姜素诱导的增殖抑制和凋亡促进作用被消除。同时，高良姜素增加了MGC 803细胞中ROS的积累，降低了Nrf2和NQO-1的表达，但提高了HO-1的表达。NAC是一种ROS清除剂，可挽救高良姜素引起的ROS过度积累和增殖抑制。STAT3过表达也可抵消高良姜素诱导的ROS过度积累。与体外实验一致，在接种MGC 803细胞的裸鼠中，高良姜素抑制肿瘤生长，并逆转了异常表达的蛋白质，如p-JAK2、p-STAT3、Bcl-2、裂解的caspase-3、裂解的PARP和Ki67。综上所述，高良姜素可能通过诱导细胞凋亡和减少细胞增殖来抑制MGC 803细胞的生长，这可能是通过调节STAT3/ROS轴介导的。我们的研究结果表明高良姜素在胃癌治疗中可能具有低毒性的潜在应用价值。
