Cancer cells can change metabolic pathways, including glycolysis and glutamine metabolism, and produce the raw materials needed for rapid proliferation and survival. Therefore, research on metabolic pathways of cancer cells might help find the targets of cancer therapy. In this review, we outlined the metabolic features of aerobic glycolysis, glutamine metabolism and (tricarboxylic acid) TCA cycle in cancer. We also described metabolic targets for cancer therapy and therapeutic agents for the corresponding targets in these metabolic pathways, and finally discussed some of the challenges related to tumor metabolism as a therapeutic target in cancer therapy.

Objective To investigate the role of T-type calcium channel in lidocaine-induced neuronal cytotoxicity . Methods SH-SYSY cell line was a gift from cell biology laboratory of our medical university. The cells were cultured in DMEM liquid culture medium at 37℃ in incubator filled with 5% CO2 , and randomly divided into 4 groups ( n = 66 each) : control group (group C)and M, L and ML groups were exposed to 5 μmol/L mibefradil (a T-type calcium channel blocker), 10 mmol/L lidocaine and 5 μmoL/L mibefradil + 10 mmol/L lidocaine for 24 h. Cell morphology was examined by electronic microscopy at 24 h of drug exposure. Cell viability (by MTT) and neuronal apoptosis (by flow cytometry) were detected immediately before and at 1, 6, 12 and 24 h of exposure to mibefradil or/and lidocaine.Results In C and M groups, the cells demonstrated dendritic protrusions, enlarged nerve processes and dense lattice. After being exposed to lidocaine for 24 h, the dendritic protrusions disappeared,the cells decreased in size, shrinked and became round; the cell viability was significantly decreased while the neuronal apoptosis increased. The lidocaine-induced changes were significantly attenuated by co-incubation with mibefradil. ConclusionT-type calcium channel is involved in lidocaine-induced neuronal cytotoxicity.

ObjectiveTo establish a rat model of nerve damage induced by intrathecal(IT) lidocaine.MethodsFifty-five adult male SD rats weighing 200-220 g were randomly divided into 5 groups (n =11 each):group normal control (group C); group dimethyl sulfoxide (DMSO)-the solvent(group D) and groups IT 5％,10％,15％ lidocaine (groups L5.10.15 ).IT catheter was successfully implanted without complication in groups D,L5,L1o,L15.DMSO,5％,10％ and 15％ lidocaine 20 μl were injected IT in groups D,L5,L10,L15 respectively.Motor dysfunction of hindlimb was assessed and scored (0 =normal,2 =complete block) and paw withdrawal threshold to mechanical stimulation (von Frey filaments) (MWT) and paw withdrawal latency to thermal nociceptive stimulus (TWL) were measured before (baseline) and at 1,2,3,4,5,7 d after IT administration in 8 animals in each group.Three animals in each group were sacrificed at 1 d after IT administration.The lumbar segment (L4-5) was removed for microscopic examination.ResultsThere was no significant difference in motor dysfunction score,MWT and TWL among groups C,D and L5.MWT was significantly increased and TWL prolonged at 1 and 2 d after IT administration in group L10,while in group L15 motor dysfunction score was significantly increased at 1,2 d after IT administration and MWT was significantly increased and TWL prolonged at 1,2,3 d after IT administration.There was significant histologic damage to spinal cord in groups L10 and L15.Conclusion Nerve damage can be induced by IT 10％ lidocaine.

Objective To evaluate the role of calcium/calmodulin-dependent protein kinase Ⅱ (CaMK Ⅱ) in the neuronal damage induced by lidocaine.Methods SH-SY5Y cells were seeded in 96-well plates (100 μl/hole) with a density of 5 × 105/ml and randomly divided into 4 groups (n =63 each):normal culture group (C group),CaMK Ⅱ inhibitor KN93 (K group),lidocaine group (L group) and KN93 + lidocaine group (KL group).KN93 (final concentration 1 μmol/L) was added to the culture medium and the cells were then cultured for 24 h in group K.Lidocaine (final concentration 10 mmol/L) was added to the culture medium and the cells were then cultured for 24 h in group L.KN93 (final concentration 1 μmol/L) and lidocaine (final concentration 10 mmol/L) were added to the culture medium and the cells were then cultured for 24 h in group KL.The cell morphology was examined with microscope after 24 h of incubation.The viability of cells was measured by MTT assay before incubation and at 1,6,12 and 24 h of incubation.The apoptosis in the cells was assessed by flow cytometry.The apoptotic rate was calculated.Results Compared with C and K groups,the cell viability was significantly decreased and the apoptotic rate was increased in L and KL groups (P ＜ 0.05).The cell viability was significantly higher and the apoptotic rate was lower in group KL than in group L (P ＜ 0.05).There was no significant difference in the cell viability and apoptotic rate between C group and K group (P ＞ 0.05).The pathological changes were obviousin group L and significantly reduced in group KL.Conclusion CaMK Ⅱ is involved in the neuronal damage induced by lidocaine.

Objective To observe the expression of calcium/calmodulin dependent protein kinase Ⅱ (CaMK Ⅱ) in the spinal cord of the rats followed lidocaine hydrochloride intrathecal injection.Methods 48 male SD rats weight(230 ± 20) g,after intrathecal indwelling catheter,were randomly divided into four groups (n =12,8 rats for behavioral detection and 4 rats for western blotting):normal group (C group),sham group (S group),DMSO group (D group),10％ lidocaine group (L group).Mechanical withdrawal threshold(MWT) and thermal withdrawal latency(TWL) were detected before and after 2 h,4 h,8 h,12 h,1 d,2 d,3 d,4 d and 5 d with drug treatment.Intumescentia lumbalis of the spinal cord were collected to measure the expression of CaMK Ⅱ with western blotting after drug treatment for 12 h.Results The based MWT of the rats in C,S and D group were (11.2 ± 3.1) g,(11.8 ± 2.2) g and (11.4 ± 2.4) g respectively.There were no differences among the every time points (n=8,P＞0.05).The MWT of the rats in L group significantly increased at 2 h,4 h,8 h,12 h,1 d,2 d,3 d and 4 d after treatment with lidocaine hydrochloride,and the data were (22.0 ± 6.6) g,(22.2 ± 5.3) g,(20.5 ±5.8)g,(18.5 ±4.3)g,(16.7 ±3.2)g,(15.2 ±3.1)g,(15.5 ±3.5)g,(13.7 ±2.4)g respectively (n=8,P＜0.01).TWL had no difference among the rats in C,S,and D group(n=8,P＞0.05).The TWL of the rats in L group significantly increased at 2 h,4 h,8 h,12 h,1 d,2 d and 3 d after treatment with lidocaine hydrochloride(n =8,P＜ 0.01).The expression of CaMK Ⅱ of the rats in C group,S group,D group and L group were 0.17 ± 0.03,0.16 ± 0.03,0.19 ± 0.05,0.42 ± 0.11,and significantly upregulated in L goup (n =4,P ＜ 0.01).Conclusion Lidocaine hydrochloride intrathecal injection can increase the expression of the CaMK Ⅱ in the spinal cord of the rats.Those indicate that CaMK Ⅱ may be involved with the nerve damage induced by lidocaine hydrochloride.