Role and mechanism of interleukin-13, interleukin-13 receptor α2 and 11β hydroxysteroid dehydrogenase 2 signaling pathways in liver metastasis of colon cancer / 中国综合临床

ABSTRACT

Objective:To investigate the role of interleukin-13(IL-13), interleukin-13 receptor α2(IL-13Rα2) and 11 β -hydroxysteroid dehydrogenase 2(11βHSD2) signaling pathway in liver metastasis of colon cancer and its mechanism.Methods:A retrospective case-control study was conducted to analyze the clinical data of 80 patients with colorectal cancer who were operated in Tongji Hospital Affiliated to Tongji Medical College of Huazhong University of Science and Technology from January 2015 to December 2018.All patients were followed up by clinic or telephone until August 30, 2019.According to the occurrence of liver metastasis, the patients were divided into metastasis group ( n=22) and non metastasis group ( n=58). Real-time fluorescence quantitative Polymerase Chain Reaction(PCR) and Western blotting were used to detect and compare the mRNA relative expression and protein expression of IL-13, IL-13Rα2, 11βHSD2, cyclooxygenase 2(COX 2) and protein kinase B in cancer tissues and cancer adjacent tissues. Glycyrrhetinic acid, an inhibitor of 11 β HSD2, was used to inhibit the activity of 11hsd2 in human colon cancer cell line HCT-8.The mRNA relative expression and protein expression of IL-13, IL-13Rα2, 11βHSD2, COX 2 and protein kinase B were detected by real-time fluorescence quantitative PCR and Western blotting before and 24 hours after glycyrrhetinic acid addition. Results:The mRNA relative expression of IL-13(0.79±0.11, 0.40±0.10), IL-13Rα2(0.72±0.13, 0.46±0.11), 11βHSD2(0.84±0.26, 0.60±0.08), COX 2(0.70±0.25, 0.37±0.04), protein kinase B (0.76±0.13, 0.42±0.06) in colon cancer tissues of metastatic and non metastatic groups were higher than those in cancer adjacent tissues(0.09±0.01, 0.10±0.06, 0.09±0.02, 0.09±0.03, 0.09±0.01, 0.09±0.02, 0.13±0.02, 0.12±0.07, 0.05±0.02, 0.05±0.03). The difference was statistically significant (t value was 28.36, 23.20, 22.07, 24.88, 16.47, 16.47, 47.86, 18.55, 24.55, 26.20, 44.40, all P<0.001). The protein expression of IL-13(0.48±0.11, 0.32±0.07), IL-13Rα2(0.52±0.11, 0.36±0.11), 11βHSD2(0.63±0.12, 0.48±0.11), COX2(0.45±0.15, 0.27±0.09), protein kinase B(0.50±0.12, 0.29±0.08) in colon cancer tissues of metastatic and non metastatic groups were higher than those in cancer adjacent tissues(0.12±0.02, 0.13±0.01, 0.10±0.02, 0.10±0.02, 0.14±0.06, 0.13±0.05, 0.10±0.03, 0.10±0.04, 0.10±0.03, 0.10±0.02). The difference was statistically significant ( t value were 15.63, 21.15, 17.71, 17.28, 11.01, 18.14, 10.55, 13.12, 15.76 and 18.90 respectively, all P<0.001). The relative expression of mRNA and protein in metastasis group was higher than that in non metastasis group ( t=15.15, 3.01, 8.97, 2.52, 6.34, 2.26, 9.82, 2.52, 16.02, 3.57, respectively, all P< 0.05). Compared with that those of before glycyrrhetinic acid addition, after 24 hours of glycyrrhetinic acid addition, the mRNA relative expression and protein expression of IL-13, IL-13Rα2 had no significant change (all P>0.05), while the mRNA relative expression and protein expression of COX 2 and protein kinase B(before adding 0.725±0.159, 0.639±0.162, 0.741±0.178, 0.668±0.145, after adding 0.108±0.085, 0.116±0.048, 0.122±0.063, 0.119±0.066) were decreased( t value were 18.744, 16.954, 17.956, 18.875 respectively , all P<0.01). Conclusion:The activation of IL-13/IL-13α2/11βHSD2 signaling pathway can promote liver metastasis of colon cancer.The mechanism may be that 11βHSD2 over expression promotes cancer cells invasion and migration-related COX2 expression and PI3K/protein kinase B pathway, and promotes liver metastasis of colon cancer.