https://blog.superhyydl.org/tags/%E7%94%B2%E7%A1%AB%E6%B0%A8%E9%85%B8%E4%BB%A3%E8%B0%A2/Recent content in 甲硫氨酸代谢 on Superhyydl's BlogHugozh-cnTue, 01 Sep 2026 00:00:00 +0000https://blog.superhyydl.org/reading/methionine-restriction-plus-vitamin-b12-antagonism/Tue, 01 Sep 2026 00:00:00 +0000https://blog.superhyydl.org/reading/methionine-restriction-plus-vitamin-b12-antagonism/<h2 id="一句话亮点">一句话亮点</h2> <p>这篇《Cancer Letters》上的文章发现，那些不怕甲硫氨酸剥夺的“甲硫氨酸非依赖”肿瘤细胞，其实是通过维生素B12依赖的MTR酶实现“甲硫氨酸自给自足”。单纯限制甲硫氨酸没用，但加上B12剥夺就能产生协同杀伤，体内实验也证实了这一点。</p> <h2 id="背景痛点">背景/痛点</h2> <p>甲硫氨酸限制抗癌这事儿，体外和动物模型效果一直不错，但临床上总是不温不火。一个可能的原因是：肿瘤内部的甲硫氨酸依赖性并不均一。有些细胞压根儿不依赖外源甲硫氨酸，被称作“甲硫氨酸非依赖”，它们可能是导致治疗抵抗的元凶。</p> <h2 id="推理链分步拆解">推理链分步拆解</h2> <h3 id="1-证实甲硫氨酸非依赖确实存在且是个普遍现象">1. 证实甲硫氨酸非依赖确实存在，且是个普遍现象</h3> <p>作者首先用了几种经典的肺癌和胰腺癌细胞系，确认了确实存在甲硫氨酸依赖（SKLU1, BxPC3）和非依赖（A427, PANC1）的细胞。更有意思的是，他们在两位肺癌患者的原代肿瘤细胞中也观察到了类似差异——一位患者的肿瘤细胞对甲硫氨酸剥夺敏感，另一位则完全不受影响。</p> <p><img alt="Fig. 1：Heterogeneous methionine dependence in cancer cell lines and primary human tumors A-E. Cell proliferation (confluence relative to baseline after cell adhesion) over 5 days under four culture conditions: Hcyst−/Met+ (methionine-supplemented), and Hcyst+/Met− (methionine-free, also called noMet medium), Hcyst−/Met− (negative control), and Hcyst+/Met+ (positive control). Methionine dependence was observed in SKLU1 (A) and BxPC3 (C), while A427 (B) and PANC1 (D) proliferated similarly with or without methionine, indicating methionine independence. E-F. Viability of freshly dissociated lung adenocarcinoma cells from two patients cultured for 3 days under methionine-supplemented (Hcyst−/Met+) or methionine- deprived (Hcyst+/Met−) conditions, assessed by resazurin assay. In patient #1 cancer cells (E), viability was significantly reduced upon methionine deprivation, consistent with methionine dependent subpopulations, while patient #2 cancer cells (F) showed no viability change, consistent with methionine independence. Data are presented with mean ± SD. Statistical significance determined by Student&rsquo;s t-test. Hcyst: Homocysteine; Met: Methionine; ns: not significant; p &lt; 0.05; p &lt; 0.01; p &lt; 0.001." loading="lazy" src="https://blog.superhyydl.org/images/reading/methionine-restriction-plus-vitamin-b12-antagonism/figure-01.png"></p>