Low-Dose Paclitaxel Inhibits Tumor Cell Growth by Regulating Glutaminolysis in Colorectal Carcinoma Cells.
Low-Dose Paclitaxel Inhibits Tumor Cell Growth by Regulating Glutaminolysis in Colorectal Carcinoma Cells.
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低剂量紫杉醇通过调节结直肠癌细胞中的谷氨酰胺分解抑制肿瘤细胞生长
DOI：
10.3389/fphar.2017.00244
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发表时间：
2017
影响因子：
5.6
通讯作者：
Zhao HY
中科院分区：
文献类型：
--
作者：
Lv C;Qu H;Zhu W;Xu K;Xu A;Jia B;Qing Y;Li H;Wei HJ;Zhao HY
紫杉醇（PTX）是一种从短叶红豆杉树皮中分离出来的天然生物碱，目前用于治疗多种肿瘤。最近，人们发现低剂量PTX是一种很有前途的治疗某些癌症的方法，副作用很少。然而，低剂量PTX（<1 nM）的抗肿瘤机制很少被阐明。在此，我们报道了低剂量PTX对大肠癌细胞的一种新的抗肿瘤机制。我们用0.1和0.3 nM的PTX处理结肠直肠癌HCT 116细胞0、1、2或3天，发现低剂量PTX抑制细胞生长而不改变细胞形态和细胞周期。在含有0.3nM PTX的培养基中持续3天pH显著降低。此外，乳酸产生以剂量和时间依赖性方式显著增加。低剂量PTX处理后，大肠癌细胞中GLS、SLC 7A 11和SLC 1A 5的表达明显降低。同时，p53和p21蛋白的表达水平在大肠癌细胞如此处理显着增加。综上所述，低剂量PTX下调了β-内酰胺酶相关基因，并增加了其乳酸产生，导致肿瘤微环境pH值降低，抑制了肿瘤细胞生长。p53和p21在低剂量PTX处理的结直肠癌细胞中的上调也有助于抑制肿瘤细胞的生长。
Paclitaxel (PTX) is a natural alkaloid isolated from the bark of a tree, Taxus brevifolia, and is currently used to treat a variety of tumors. Recently, it has been found that low-dose PTX is a promising treatment for some cancers, presenting few side effects. However, antitumor mechanisms of low-dose PTX (<1 nM) have rarely been illuminated. Here we report a new antitumor mechanism of low-dose PTX in colorectal carcinoma cells. We treated colorectal carcinoma HCT116 cells with PTX at 0.1 and 0.3 nM for 0, 1, 2, or 3 days, and found that low-dose PTX inhibits cell growth without altering cell morphology and cell cycle. There was a significant decrease of pH in culture media with 0.3 nM PTX for 3 days. Also, lactate production was significantly increased in a dose- and time-dependent manner. Furthermore, expression of glutaminolysis-related genes GLS, SLC7A11 and SLC1A5 were significantly decreased in the colorectal carcinoma cells treated with low-dose PTX. Meanwhile, protein expression levels of p53 and p21 increased significantly in colorectal carcinoma cells so treated. In summary, low-dose PTX down-regulated glutaminolysis-related genes and increased their lactate production, resulting in decreased pH of tumor microenvironments and inhibition of tumor cell growth. Up-regulation of p53 and p21 in colorectal carcinoma cells treated with low-dose PTX also contributed to inhibition of tumor cell growth.