Chen Jen-Lung, Ma Yi-Shih, Tsai Kuen-Jang, Tsai Hsin-Yi, Yeh Li-Jen, Tsai Hung-Wen, Yen Judy, Tsai Hong-Wen, Lin Ming-Wei
Department of Surgery, E-Da Hospital, I-Shou University, Kaohsiung 82445, Taiwan.
Department of Chinese Medicine, E-Da Cancer Hospital, I-Shou University, Kaohsiung 82445, Taiwan.
Curr Issues Mol Biol. 2025 Aug 12;47(8):646. doi: 10.3390/cimb47080646.
Although chemotherapy is the preferred treatment for gastric cancer, the therapeutic drugs currently available have limited efficacy and severe side effects. Cancer stem cells within tumor masses have the distinctive properties of self-renewal, maintenance, and resistance to chemotherapy. Hence, agents capable of targeting stemness in gastric tumors with minimal side effects are urgently required. Enzymes that generate reactive oxygen species contribute to the high oxidation levels observed in tumors. Additionally, nuclear factor erythroid 2-related factor 2 (Nrf2), an antioxidant transcription factor, regulates cancer stemness. Increasing evidence highlights the potential of nutritional supplementation to treat cancer stemness. ω-3 polyunsaturated fatty acids support human health and offer benefits for cancer treatment. Linolenic acid (LA), an ω-3 polyunsaturated fatty acid, inhibits the expression of proteins associated with stemness and promotes apoptosis in gastric cancer cells. Our findings indicated that LA treatment substantially inhibited key characteristics of gastric cancer stemness and induced oxidative stress and caspase-3-mediated apoptosis by downregulating Nrf2-mediated expression. These results suggest that LA is a promising nutritional supplement for targeting cancer stemness in the treatment of gastric cancer.
尽管化疗是胃癌的首选治疗方法，但目前可用的治疗药物疗效有限且副作用严重。肿瘤块内的癌症干细胞具有自我更新、维持和对化疗耐药的独特特性。因此，迫切需要能够以最小副作用靶向胃肿瘤干性的药物。产生活性氧的酶会导致肿瘤中观察到的高氧化水平。此外，抗氧化转录因子核因子红细胞2相关因子2（Nrf2）调节癌症干性。越来越多的证据凸显了营养补充剂治疗癌症干性的潜力。ω-3多不饱和脂肪酸有益于人类健康，并对癌症治疗有帮助。ω-3多不饱和脂肪酸亚麻酸（LA）可抑制与干性相关的蛋白质表达，并促进胃癌细胞凋亡。我们的研究结果表明，LA处理可显著抑制胃癌干性的关键特征，并通过下调Nrf2介导的表达诱导氧化应激和半胱天冬酶-3介导的凋亡。这些结果表明，LA是一种有前景的营养补充剂，可在胃癌治疗中靶向癌症干性。
