ABSTRACT
OBJECTIVE To investigate the effects of GSTP1， XRCC1， ABCB1， MTHFR gene polymorphisms on efficacy and toxic effect of chemotherapy regimen containing oxaliplatin in patients with stage Ⅲ and Ⅳ colorectal cancer patients. METHODS Clinical data of 76 patients with stage Ⅲ and Ⅳ colorectal cancer who received chemotherapy regimen containing oxaliplatin （XELOX，FOLFOX） were collected from the Second Affiliated Hospital of Soochow University from September 2018 to March 2020. The correlation of genotypes with progression-free survival （PFS） and toxic effect was analyzed by using univariate and multivariate COX regression model. RESULTS Carriers of the ABCB1 3435T＞C locus C allele （TC/CC） had a significantly higher risk of progression compared to TT genotype patients [HR＝2.39， 95%CI （1.05，5.50）， P＝0.038]. The risk of progression in patients at stage Ⅳ was significantly higher than those at stage Ⅲ [HR＝8.11， 95%CI（3.39，19.40）， P＜0.001]. Chemotherapy regimen， Karnofsky performance status score and tumor site had no significant effect on disease progression （P＞0.05）. Mutations in gene loci were not correlated with adverse reactions （P＞0.05）. CONCLUSIONS Patients carrying ABCB1 TC/CC and receiving chemotherapy regimen containing oxaliplatin have a higher risk of disease progression， which may be associated with longer PFS in patients （TT genotype） with stage Ⅳ colorectal cancer receiving the chemotherapy， while GSTP1， XRCC1， and MTHFR gene polymorphisms have no significant impact.
ABSTRACT
Background: Oxidative stress is crucial for the development of ionizing radiation-induced intestinal injuries and inflammation. Taurine is a sulfur-containing amino acid distributed in tissues and organs throughout the body. It possesses several important physiological functions, including anti-oxidative activity and anti-inflammatory effects. Aims: To investigate the therapeutic effect and underlying mechanism of taurine against radiation-induced intestinal injuries. Methods: CCK-8 assay and DCFH-DA, a fluorescence probe of intracellular reactive oxygen species (ROS) were applied to determine the effects of taurine on radiation-induced inhibition of cell viability and ROS accumulation in human intestinal epithelial cell line HIEC-6. The modulatory effects of taurine on expressions of oxidative stress-related genes in intestinal cells after exposure to radiation were measured by real-time PCR in in vitro and in vivo studies. The roles of taurine in maintenance of intestinal morphology and suppression of cell apoptosis in mice receiving whole body radiation were assessed by HE staining and TUNEL staining. Results: In in vitro study, taurine improved the radiation-induced inhibition of cell viability and reduced intracellular ROS accumulation in HIEC-6 cells. The expression levels of catalase (CAT) and glutathione peroxidase 1 (GPx1) in HIEC-6 cells were up-regulated by taurine treatment. In vivo study showed that taurine activated the nuclear factor erythroid 2-related factor 2/heme oxygenase-1 (Nrf2/HO-1) signaling pathway, alleviated intestinal villi disorganization and loss of crypt cells, and suppressed cell apoptosis in mice after radiation. Conclusions: Taurine can reduce the intracellular ROS accumulation via activating Nrf2/HO-1 antioxidant signaling pathway, and thereby, exerts protective effect against radiation-induced intestinal injuries. It might be a candidate for treatment of intestinal injuries in patients undergoing radiotherapy.