Glycogenes mediate the invasive properties and chemosensitivity of human hepatocarcinoma cells

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• 作者：Rui Guo^a ; ¹ ; Lei Cheng^b ; ¹ ; Yongfu Zhao^c ; Jianing Zhang^d ; Chunqing Liu^a ; Huimin Zhou^e ; Li Jia^a ; ^{jiali@dlmedu.edu.cn}
• 关键词：5-FU TM ; 5-fluorouracil tunicamycin ; PBS ; phosphate-buffered saline ; PBST ; PBS containing 0.1 % Tween 20 ; TBS ; tris buffered saline ; DMSO ; dimethyl sulfoxide ; PNGase F ; peptide N glycosidase F ; IR ; tumor inhibition rate
• 刊名：The International Journal of Biochemistry and Cell Biology
• 出版年：2013
• 出版时间：February, 2013
• 年：2013
• 卷：45
• 期：2
• 页码：347-358
• 全文大小：1758 K

文摘

Aberrant cell-surface glycosylation patterns are present on tumors and have been linked to tumor progression. This study aimed to identify the alterations of glycogene and N-glycan involved in tumor invasion, tumorigenicity and drug resistance in MHCC97-H and MHCC97-L human hepatocarcinoma cell lines, which have high, low metastatic potential, respectively. Using real-time PCR for quantification of glycogene and FITC-lectin binding for glycan profiling, we found that the expression of glycogenes and glycan profiling were different in MHCC97-H cells, as compared to those in MHCC97-L cells. We silenced the expression levels of glycogenes MGAT3 and MGAT5, which were over-expressed in MHCC97-L and MHCC97-H cells. Knockdown of MGAT3 expression promoted MHCC97-L cells invasion and increased resistance to 5-fluorouracil in vitro. The silencing of MGAT5 in MHCC97-H cells inhibited invasion and increased sensitivity to 5-fluorouracil in vitro. Further analysis of the N-glycan regulation by tunicamycin application or PNGase F treatment in MHCC97-H and MHCC97-L cells showed partial inhibition of N-glycan glycosylation, decreased invasion, tumorigenicity and increased sensitivity to 5-fluorouracil both in vitro and in vivo. These findings suggest that alterations of glycogene and N-glycan in human hepatocarcinoma cells correlate with tumor invasion, tumorigenicity and sensitivity to chemotherapeutic drug, and have significant implications for the development of treatment strategies.