目的 基础实验及临床研究均证实KD具有一定的抗肿瘤作用，但是疗效并不一致，尚没有特异性的分子靶标或明确的适应证来衡量其抗肿瘤作用。本研究拟检测多种肿瘤细胞系酮体代谢酶的表达情况，以验证不同酮体代谢酶表达水平的肿瘤细胞对KD治疗的敏感性。方法 通过qRT-PCR检测33株肿瘤细胞系BDH1和OXCT1编码基因的表达情况。根据筛选结果选择BDH1和OXCT1高表达的HeLa细胞以及低表达PANC-1细胞进行KD敏感性的体内外验证。使用手持式细胞计数器检测含不同浓度βHB的低糖培养基中HeLa和PANC-1细胞增殖情况。然后， 敲低HeLa细胞中BDH1和OXCT1的表达水平，构建HeLa和PANC-1裸鼠皮下移植瘤， 体内外重新验证KD抗肿瘤治疗的敏感性。结果 与对照组相比，低糖组HeLa细胞和PANC-1细胞增殖明显受抑制，但是低糖培养基加入βHB后，HeLa细胞增殖明显好转，但是PANC-1细胞增殖无显著好转。动物实验中，KD显著抑制PANC-1移植瘤的生长，但是对HeLa移植瘤的生长无抑制作用，而同时敲低BDH1和OXCT1的HeLa细胞对KD治疗敏感。结论 酮体代谢关键酶BDH1和OXCT1低表达，并且无明显诱导的肿瘤对生酮代谢疗法敏感。

Objective Although ketogenic diet (KD) has been studied its certain anti-tumor effect by basic research and clinical trials, the specific molecular targets or indications which verify its anti-tumor activity are lack. In this study, we examined the expression of different ketolytic key enzymes to identify the sensitivity of KD in tumor cells. MethodsExpression of genes encoding 3-hydroxybutyrate dehydrogenase 1 (BDH1) and succinyl-CoA: 3-oxoacid CoA transferase 1 (OXCT1) have been determined in 33 human cancer cell lines by quantitative RT-PCR. HeLa cell and pan-1 cell were selected with high expressing and low expressing two enzymes respectively. Proliferation of HeLa and PANC-1 cells was determined by using a hand-held automatic cell counter after cultured in low glucose medium with or without DL-β-Hydroxybutyric acid sodium salt (βHB). BDH1 and OXCT1 were knocked down in HeLa cells by lentivirus-mediated RNA interference and established HeLa and PANC-1 cell xenograft tumors models in BALB/C nude mice to identify the sensitivity of KD in anti-tumor therapy. Results Compared to control group, proliferation of HeLa and PANC-1 cells in low glucose (LG) was significantly inhibited. Howevere, proliferation of HeLa cells was significantly increased, while added βHB into LG group, but there was no significant effect on proliferation of PANC-1 cells. Animal experiments demonstrated that KD inhibited growth of PANC-1 cell xenograft tumors dramatically, but no effect on the growth of HeLa xenograft tumor. Down-regulation of both BDH1 and OXCT1 in HeLa cells rendered their sensitivity to KD in vitro and in vivo. ConclusionsTumors with low expression of ketolytic enzymes which are not obviously induced gene expression are sensitive to ketogenic metabolic therapy.