CHST11and CHST13Regulate The Invasive Properties And Chemosensitivity Of Human Hepatocellular Carcinoma

Objective:This study aimed to clarify the association of CHST11-13expressionwith metastasis and drug sensitivity in hepatocellular carcinoma (HCC) cells.Methods:(1)Using real-time PCR for quantification of CHST11-13genes, we comparedthe differential expression (i.e.,>3-fold higher) of CHST11-13genes in the4HCCcell lines (HepG2, BEL7402, MHCC97-L and MHCC97-H) and the immortalizedliver cell line (L02) as well as HCC and transitional tissues from patients.(2)Manipulating the differentially expressed CHST genes, to detect the invasiveability and the chemosensitivity to anti-tumor drugs in vitro and in vivo. The effect ofaltered expression of CHST genes on the activity of MAPK signaling pathway wasalso observed.(3)Blocking the MAPK pathway by its specific inhibitors, the invasive andability the chemosensitivity of MHCC cells was analyzed.Results:(1)Significantly reduced levels of CHST11and CHST13were observed in highlyinvasive MHCC97-H cells compared with those of MHCC97-L cell line with lowmetastatic potential.(2)Decreased or forced expression of CHST11and CHST13led to increasedmetastatic phenotype and decreased drug sensitivity of MHCC97-L and MHCC97-H cells，opposite results were obtained when we treated MHCC97-H cells with CHST11or CHST13expression vector.(3)Pharmacologic inhibition of the MAPK pathway suppressed invasivepotential and increased drug sensitivity of MHCC97-H cells.Conclusion:(1) The expression of CHST11and CHST13genes was different in differentialcell lines. These characteristic alterations are associated with the invasive ability andchemosensitivity in HCC.(2) CHST11and CHST13negatively mediate metastasis and drug resistance ofHCC cells probably by regulating the oncogenic MAPK activity, which might havesignificant implications for the development of treatment strategies.