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Aim:We have reported novel anticancer bioactive peptides (ACBPs) that show tumor-suppressive activities in human gastric cancer, leukemia, nasopharyngeal cancer, and gallbladder cancer. In this study, we investigated the effects of ACBPs on human colorectal cancer and the underlying mechanisms.Methods:Cell growth and apoptosis of human colorectal tumor cell line HCT116 were measured using cell proliferation assay and flow cytometry, respectively. The expression levels of PARP, p53 and Mcl1A were assessed with Western blotting and immunohistochemistry. For evaluation of the in vivo antitumor activity of ACBPs, HCT116 xenograft nude mice were treated with ACBPs (35 μg/mL, ip) for 10 days.Results:Treatment of HCT116 cells with ACBPs (35 μg/mL) for 4–6 days significantly inhibited the cell growth. Furthermore, treatment of HCT116 cells with ACBPs (35 μg/mL) for 6–12 h significantly enhanced UV-induced apoptosis, increased the expression of PARP and p53, and decreased the expression of Mcl-1. Administration of ACBPs did not change the body weight of HCT116 xenograft nude mice, but decreased the tumor growth by approximately 43%, and increased the expression of PARP and p53, and decreased the expression of Mcl-1 in xenograft mouse tumor tissues.Conclusion:Administration of ACBPs inhibits human colorectal tumor cell growth and induces apoptosis in vitro and in vivo through modulating the PARP-p53-Mcl-1 signaling pathway.

To investigate the relationship between NAD(P)H:quinone oxidoreductase 1 (NQO1) C609T polymorphism and colon cancer risk in farmers from western region of Inner Mongolia.Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) was performed to analyze NQO1C609T polymorphism from 160 healthy controls and 76 colon cancer patients.Among the colon cancer patients, the incidence of NQO1T allele (53.29%) was significantly higher than it in control group (33.75%, P<0.001). The individuals with NQO1 T allele had higher risk [2.239 (95% CI: 1.510–3.321) times] to develop colon cancer than individuals with NQO1 C allele. The incidence of NQO1 (T/T) (34.21%) in colon cancer patients was higher than that in control group (15.62%, P<0.001). Odds ratios (OR) analysis suggested that NQO1(T/T) and NQO1(T/C) genotype carriers had 3.813 (95% CI: 1.836–7.920) times and 2.080 (1.026–4.219) times risk compared with wild-type NQO1(C/C) gene carriers in developing colon cancer. Individuals with NQO1(T/T) genotype had 2.541 (95% CI: 0.990–6.552) times, 3.713 (95% CI: 1.542–8.935) times, and 3.471 (95% CI: 1.356–8.886) times risk than individuals with NQO1(T/C) or NQO1(C/C) genotype in well-differentiated, moderately-differentiated, and poorly-differentiated colon cancer patients, respectively.NQO1gene C609T could be one of risk factors of colon cancer in farmers from western region of Inner Mongolia.

Abstract: Objective: To explore the relationship between cytochrome P450 2E1 (CYP2E1) RsaI/PstI and DraI polymorphism and lung cancer susceptibility in Mongolian and Han population in Inner Mongolia of China. Methods: CYP2E1 RsaI/PstI and DraI polymorphisms were detected by polymerase chain reaction-restriction fragment length polymorphism in 64 lung cancer patients, 150 healthy Mongolian and 150 healthy Han individuals. The distribution of genotype and allele frequencies of CYP2E1 RsaI/PstI and DraI polymorphisms were studied. Results: The risk of lung cancer was increased in individuals with CYP2E1 (cl/cl) and CYP2E1 (DD) with OR values of 2.431 (95%CI=1.082-5.460) and 2.778 (95%CI=1.358-5.683) respectively (P<0.05). When CYP2E1 RsaI/PstI and DraI polymorphisms were combined, the risk of lung cancer was reduced in individuals with CYP2E1 (cl/c2+c2/c2 and DD+CC) with OR values of 0.233 (95%CI=0.088-0.615, P<0.05). In smokers, the susceptibility to lung cancer was higher in the individuals with CYP2E1 (c1/c1) and CYP2E1 (DD) than in the individuals with c2 and C allele (P<0.05, OR =2.643 and 4.308 respectively). There was no significant difference in distribution of CYP2E1 genotype frequency between healthy Mongolian, Han population and lung cancer patients, healthy controls in Inner Mongolia. Conclusion: CYP2E1 (c1/c1) and CYP2E1 (DD) are predisposing factors of lung cancer in population in Inner Mongolia. CYP2E1 (c2+C) co-mutation may decrease the risk of lung cancer. Smoking exerts synergetic effect with CYP2E1 (c1/c1) and CYP2E1 (DD) on the occurrence of lung cancer.

The development of intestinal gastric carcinoma involves several precancerous stages. The environmental factor plays an important role in gastric carcinogenesis, while the host's genetic makeup may influence the susceptibility to cancer. In this study we investigated correlations of the p53 variations at codon 72 and p21WAF1/CIP1 haplotype with the risk of intestinal gastric carcinoma. Forty-eight intestinal gastric carcinoma cases (GC), 96 chronic atrophic gastritis (CAG), 96 intestinal metaplasia (IM) and 96 dysplasia (DYS) controls were enrolled in this study. The p53 codon 72 proline allele carriers were found to be more susceptible to progress to GC than to IM (OR = 2.22, 95%CI = 1.05–4.70, P = 0.038). Patients carrying homozygous p21WAF1/CIP1 haplotype A, which contains the serine at codon 31, the cytidine at the 16th base of the second intron, and the cytidine at the 70th base of the exon 3 were more prone to develop GC than to reach the IM or DYS stage (IM versus GC, OR = 3.35, 95%CI = 1.11–10.15; DYS versus GC, OR = 3.27, 95%CI = 1.09–9.80, P = 0.035). The combination of p53 codon 72 variation with the p21WAF1/CIP1 haplotype further distinguished the risk of GC from IM precancerous lesion (OR = 9.31, 95% CI = 1.77–48.85, P = 0.08). These results suggest that p53 and/or p21WAF1/CIP1 genotype may influence the progression during gastric tumorigenesis.

Objective The role and mechanism of tetrathiomolybdate (TM) in cancer-associated fibroblasts (CAFs) in colon cancer using three-dimensional (3D) culture were investigated, and the associations between the focal adhesion kinase (FAK) pathway and epithelial–mesenchymal transition (EMT) in CAFs were explored.Methods A 3D co-culture model of colon cancer LOVO cells with CAFs and normal fibroblasts (NFs) was established using Matrigel as a scaffold material. The differential expression of LOXL2 (lysyl oxidase-like 2) in the supernatant of CAFs and NFs was determined using ELISA, and expression levels of EMT-related proteins and FAK signaling pathway-related proteins were determined using western blot.Results LOXL2 levels secreted by CAFs were higher compared with that secreted by NFs. In the CAF + LOVO group, compared with the LOVO group, E-cadherin expression decreased significantly, while N-cadherin and F-PAK expression increased significantly. TM results were opposite compared with the above results.Conclusions CAFs stimulate EMT in human colon cancer LOVO cells by secreting LOXL2 to activate the FAK signaling pathway, thereby promoting tumor metastasis. TM inhibited the occurrence of EMT in the CAF-induced colon cancer LOVO cell line, thereby reducing the invasion and metastasis of colon cancer cells.