Metastasis and drug resistance of human hepatocarcinoma cells mediated by glycogenes and N-glycans

Abstract

Objective To identify the relationship among glycogenes, N-glycans and hepatocarcinoma metastasis and drug resistance by studying the differential expressions of glycogenes and N-glycans in MHCC97-H and MHCC97-L human hepatocarcinoma cell lines, and to confirm the novel target of hepatocarcinoma metastasis and anti-tumor therapy. Methods Real-time PCR was used to quantitatively analyze glycogenes and fluorescein isothiocyanate （FITC）-lectin was used to analyze glycans characteristics. RNA interference approach was used to interfere the glycogenes, and the invasive ability in vitro and drug susceptibility of MHCC97-H cells were detected before and after interference. Modification of N-glycosylation （tunicamycin and PNGase F treatment） was done, and the invasiveness in vitro, tumorigenicity in vivo and drug susceptibility of MHCC97-H cells were detected be- fore and after modification. Results The expressions of glycogenes and glycans were different in MHCC97-H cells and MHCC97-L cells. The silence of MGAT5 in MHCC97-H cells inhibited invasion ability and increased sensitivity to 5-fluorouracil in vitro（ t = 7.312, P 〈 0.05）. Modification of N-glyeosylation decreased MHCC97-H cells invasion ability in vitro and tumorigenicity in vivo and increased sensitivity to 5-fluorouracil. Conclusion The differential expressions of glycogens and N-glycans in human hepatocarcinoma cell lines correlate with tumor invasion and drug resistance, and they are expected to be novel targets of tumor chemotherapy. Key words: Glycosyhransferases ; Liver neoplasms ; Neoplasm metastasis ; Drug resistance