Effect of ferroptosis inducer Erastin on apoptosis of colorectal cancer induced by Shikonin / 中国药理学通报

Aim To explore the effect of ferroptosis inducer Erastin combined with Shikonin on the anti-tumor activity of colorectal cancer cells and its mechanism.Methods Erastin(0,4,8,16,32,64 μmol·L-1)and Shikonin(SW-480:0, 0.5,1,2,4,8 μmol·L-1 with SW-620:(0,0.2,0.4,0.8,1.6,3.2 μmol·L-1)alone and 10 μmol·L-1 Erastin combined with various concentrations of Shikonin were used to treat colorectal cancer cells SW480 and SW620; Cell viability was detected by CCK-8 method and the apoptosis was detected by AnnexinV/PI double staining.The changes of active oxygen content in colorectal cancer cells were measured by ROS detection kit, and the changes of intracellular lactic acid content in SW480 and SW620 were measured by 10 μmol·L-1 Erastin alone or in combination with 2 μmol·L-1 and 1 μmol·L-1 Shikonin, respectively.The protein expressions of Bax, Bcl-2, PARP1, Caspase3,Caspase8,AKT and P-akt in SW480 and SW620 cells were detected by Western blot.Results The results of CCK-8 showed that the combination group could significantly inhibit the viability of colorectal cancer cells and the apoptotic rate was the highest.At the same time, lactic acid was inhibited most obviously.The content of intracellular reactive oxygen species and apoptosis-related proteins also changed significantly.Conclusions Erastin combined with Shikonin can synergistically induce the apoptosis of colorectal cancer cells.The mechanism may be inhibiting the production of lactic acid in tumor cells, increasing the content of reactive oxygen species in tumor cells, inhibiting the AKT signaling pathway, and activating pro-apoptotic proteins to induce colorectal cancer cell apoptosis.

Correlation Between the APOB rs1042034 SNP and Blood Lipid Characteristics of 2 Ethnic Groups in China.

The apolipoprotein (Apo) B gene (APOB) is a susceptible gene for dyslipidemia. The purpose of this investigation was to explore the relationship between the APOB rs1042034 single-nucleotide polymorphism (SNP) and serum lipid levels in the Maonan and Han populations. A total of 598 Maonan participants and 609 Han participants were genotyped by polymerase chain reaction and restriction fragment length polymorphism, and the genotypes were also verified by sequencing. There were no differences in genotype and allele frequencies between the 2 ethnic groups or between males and females. The levels of triglyceride (TG) in Maonans were higher and high-density lipoprotein cholesterol was lower in the A allele carriers than the A allele noncarriers; the A allele carriers in Hans had higher TG levels and lower ApoA1/ApoB ratio than the A allele noncarriers (P < .05 for all). Subgroup analysis showed that the A allele carriers in Maonan females had higher TG levels and the A allele carriers in Han females had higher TG levels and lower ApoA1/ApoB ratio than the A allele noncarriers (P < .05 for all). In our study populations, there may be ethnicity- and/or sex-specific associations between the APOB rs1042034 SNP and serum lipid levels.

Association between the MVK rs2287218 SNP and the risk of coronary heart disease and ischemic stroke: A case-control study.

The association between the mevalonate kinase gene (MVK) single nucleotide polymorphism (SNP) and serum lipid levels has been detected in several previous genome-wide association studies, but the results are inconsistent. In addition, it is still unclear whether the loci indentified exert the similar effect on the susceptibility of coronary heart disease (CHD) or ischemic stroke (IS). Therefore, the present study was undertaken to detect the association between the MVK rs2287218 SNP and serum lipid levels, the susceptibility of CHD and IS in a Southern Chinese Han population. The genotypes of the SNP in 1764 unrelated subjects (CHD, 583; IS, 555; and healthy controls, 626) were determined by the Snapshot technology. The genotypic and allelic frequencies were different between CHD and control subjects (P ≤ 0.013 for each), or between IS and control groups (P < 0.01 for each). The T allele carriers had an increased risk of CHD and IS (CHD: OR = 1.674, 95%CI = 1.25-2.25, P = 0.001 for CT/TT vs. CC genotypes; OR = 1.595, 95%CI = 1.23-2.07, P < 0.001 for T vs. C alleles; IS: OR = 1.890, 95%CI = 1.36-2.47, P = 0.001 for CT/TT vs. CC genotypes; OR = 1.829, 95%CI = 1.38-2.42, P < 0.001 for T vs. C alleles). The T allele carriers in healthy controls had lower serum high-density lipoprotein cholesterol (HDL-C) levels than the T allele non-carriers (P = 0.013). These findings suggest that the MVK rs2287218 SNP is likely to increase the risk of CHD and IS by decreasing serum HDL-C levels in our study populations.

Association of the LIPC rs1532085 SNP and serum lipid traits in the Chinese Maonan and Han populations.

The hepatic lipase gene (LIPC) is known to play an important role in lipid and lipoprotein metabolism pathways, but the association of the LIPC rs1532085 single nucleotide polymorphism (SNP) and serum lipid profiles has not been previously reported in different racial/ethnic groups. The present study was to detect the association of the LIPC rs1532085 SNP and several environmental factors with serum lipid levels in the Maonan and Han populations. Genotypes of the LIPC rs1532085 SNP in 833 individuals of Maonan nationality and 801 participants of Han nationality were determined by polymerase chain reaction and restriction fragment length polymorphism. The frequencies of AA, AG, and GG genotypes were 22.34%, 47.70%, and 29.96% in Han, and 24.96%, 51.38%, and 23.64% in Maonan populations (P < 0.05). The frequency of the G allele was 53.80% in Han and 49.33% in Maonan individuals (P < 0.05). The G allele carriers had lower total cholesterol (TC), triglyceride (TG), low-density lipoprotein cholesterol (LDL-C), Apolipoprotein (Apo) A1 and ApoB levels in Han than the G allele non-carriers, but not in Maonan. Subgroup analyses indicated that the G allele carriers had lower TC, TG, LDL-C and ApoA1 levels in Han females than the G allele non-carriers (P < 0.05-0.001). Serum lipid parameters in the two ethnic groups were also associated with several environmental factors. These findings revealed that there might be a racial/ethnic- and/or sex-specific association between the LIPC rs1532085 SNP and serum lipid parameters in some populations.