Centre of Research and Continued Engineering Development, North-West University, Silver Lakes, South Africa; TEMM International (Pty) Ltd, Pretoria, South Africa.
Department of Physiology, University of Pretoria, Pretoria, South Africa.
Nutrition. 2020 Jun;74:110748. doi: 10.1016/j.nut.2020.110748. Epub 2020 Jan 25.
Although metabolic treatment of highly glycolytic cancers and metastases is becoming an important research field, the effects of such treatments are not fully quantified yet. In this article we attempt to quantify the effect of long-term glucose deprivation (similar to ketogenic diets) on cancer cells using in vitro tests.
Two tumorigenic cell lines were used, namely a metastatic breast and a cervical cancer cell line. The non-tumorigenic control cell line was an immortalized breast cell line. All the cell lines were stabilized at a typical average human blood glucose level of 6 mmol/L. The cell lines were then exposed to the therapeutic blood glucose level of 3 mmol/L for 90 d.
The tests indicated that glucose deprivation restricted the different cancer cell lines' growth more than that of non-tumorigenic cells. The different cell lines were also differentially affected, which suggests that long-term glucose deprivation will not be equally effective for different types of cancer. The highly glycolytic breast cancer cell line was most adversely affected, with cell growth decreasing to 30% after 26 d. Cell growth was stable at this level for up to 22 d. Furthermore, all of the other cancer cell lines were similarly affected.
This in vitro data could help to direct future human in vivo tests to find the most therapeutic time (cancer cells at their most vulnerable) for additional short-term adjuvant therapies. Partial recovery of proliferation occurred after 90 d. Therefore, as expected, the results also indicated that without an adjuvant treatment, full extinction cannot be reached with the proposed long-term metabolic treatment. The need for more clinical data on long-term glucose deprivation treatments for cancer is well described in the literature. This paper attempts to add to the available pool of knowledge.
尽管针对高度糖酵解癌症和转移灶的代谢治疗正成为一个重要的研究领域,但此类治疗的效果尚未得到充分量化。本文试图通过体外试验来量化长期葡萄糖剥夺(类似于生酮饮食)对癌细胞的影响。
使用了两种致瘤细胞系,即转移性乳腺癌和宫颈癌细胞系。非致瘤对照细胞系是永生化的乳腺细胞系。所有细胞系均稳定在典型的平均人体血糖水平 6mmol/L。然后将细胞系暴露于治疗性血糖水平 3mmol/L 下 90 天。
测试表明,葡萄糖剥夺对不同癌细胞系的生长限制比对非致瘤细胞更为严重。不同的细胞系也受到不同程度的影响,这表明长期葡萄糖剥夺对不同类型的癌症不会产生同样的效果。高度糖酵解的乳腺癌细胞系受到的影响最大,细胞生长在 26 天后降至 30%。此后,细胞生长在该水平稳定 22 天。此外,所有其他癌细胞系也受到类似的影响。
这些体外数据有助于指导未来的人体体内试验,以找到对额外短期辅助治疗最具治疗效果的时间(癌细胞最脆弱的时间)。90 天后出现增殖的部分恢复。因此,正如预期的那样,结果还表明,如果没有辅助治疗,提出的长期代谢治疗无法达到完全灭绝的效果。文献中很好地描述了对癌症进行长期葡萄糖剥夺治疗的更多临床数据的需求。本文试图为此提供更多的知识储备。